Artificial metalloenzymes as catalysts in non-natural compounds synthesis

Coordination Chemistry Reviews xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

Coordination Chemistry Reviews journal homepage: www.elsevier.com/locate/ccr

Review

Artificial metalloenzymes as catalysts in non-natural compounds synthesis Karolina Wieszczycka ⇑, Katarzyna Staszak Poznan University of Technology, Institute of Chemical Technology and Engineering, Berdychowo St. 4, 60-965 Poznan, Poland CERENA – Centre for Natural Resources and the Environment, Department of Chemical Engineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal

a r t i c l e

i n f o

Article history: Received 21 April 2017 Received in revised form 13 June 2017 Accepted 18 June 2017 Available online xxxx Keywords: Metalloenzymes Catalyst Organic synthesis

a b s t r a c t The status of high-accuracy studies of metalloenzymes application as catalysts in non-natural compounds synthesis has been presented. The discussion is organized based on their stereo- and regioselectivities, as well as catalytic activities and the majority of these examples were reported within the last few years. Moreover computational methods, which are helpful for further development of new artificial metalloenzyme catalyst systems and explanation of the reaction mechanism, are discussed. Ó 2017 Elsevier B.V. All rights reserved.

Contents 1. 2. 3. 4.

5. 6.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Metalloenzymes – basic principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Artificial metalloenzymes with immobilized metals complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Recent advances in synthesis with artificial metalloenzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Oxidation and hydroxylation of olefins and benzyl moieties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Hydrogenation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Olefin metathesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4. Diels–Alder reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5. Friedel–Crafts alkylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6. Transfer reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Modelling of artificial metalloenzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction Coordination compounds with metals play an essential role in the life processes. Metal ions are found in one-third of all proteins [1,2]. Some metals are essentials in the biological systems, the ⇑ Corresponding author at: Poznan University of Technology, Institute of Chemical Technology and Engineering, Berdychowo St. 4, 60-965 Poznan, Poland. E-mail address: [email protected] (K. Wieszczycka).

00 00 00 00 00 00 00 00 00 00 00 00 00 00

others are considered toxic [3]. The typical properties of metal caused possibility of them to be present in the life processes [4– 6]. As it is seen in Fig. 1 metal has got charge, which can be changed depending on the coordination environment from cationic, by neutral to anionic charge. The metals have ability to interact with both organic and inorganic ligands. Depending on the ligands different properties of formed complexes can be obtained. The replacement of ligand or metal in complex structure changes the behaviour of

http://dx.doi.org/10.1016/j.ccr.2017.06.012 0010-8545/Ó 2017 Elsevier B.V. All rights reserved.

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

2

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

Fig. 1. General chemical properties of metals.

formed compounds. Moreover, the bond lengths, bond angles and number of coordination sites can vary depending on the metal and its oxidation state in the complex compound. Therefore metal–ligand complexes span a range of coordination geometries that give them unique shapes compared to organic molecules. The metal oxidation state has got implications for toxicity. For example chromium(III) ions are necessary to glucose metabolism [7], while chromium ions in the 6+ are mutagenic and carcinogenic, due to the various forms of DNA damage including DNA interstrand crosslinks, DNA-protein crosslinks, DNA strand breaks, and Cr-DNA adducts [8]. Lewis acid character of metals enables the metal ions with high electron affinity to polarize groups significantly which are coordinated to them (i.e. hydrolysis reactions). Very interesting group of metals are the transition metals with partially filled dshell or f-shell for lanthanides (sometimes called inner transition elements). The d-block metal ions readily form complexes. The complex formation often is accompanied by a change in colour and sometimes by a change in the intensity of colour. In these orbitals there are a variable number of electrons and these metals have ability to undergo 1-electron oxidation and reduction reactions. The occurrence of variable oxidation states and, often, the interconversion between them, is a characteristic of most d-block metals [9]. Moreover the complexes formed with such metals have got interesting electronic and magnetic properties. It is worth to mention that d-block metals are very often used to produce catalysts applied in chemical industry. It could be used as catalyst in wellknown reactions such as iron in the Haber process to obtain ammonium, nickel in the hydrogenation of C@C bonds, vanadium (V) oxide in conversion reaction of sulphur dioxide into sulphur trioxide, as well as new as described in [10–15]. Metals can easily lose electrons from the familiar elemental or metallic state and form positively charged ions. The cationic forms of metals are soluble in biological fluids. Moreover the metal ions, which are electron deficient, can bind and interact with electron rich molecules. Examples of such molecules are biological compounds such as proteins and DNA [16]. The metal ions present in biological systems (mainly metalloproteins) have different functions such as [17]: (i) structural (stabilization of protein chain by Zn2+ forms strong bonds to sulphur ligands, mainly from amino

acid cysteine), (ii) transmission of impulses along nerve fibres (associated with the change in K+ and Na+ concentration inside the fibre and outside pattern; Na+/K+ pomp), (iii) messenger in nerve action (Ca2+ complexes), (iv) blood clotting (Ca2+ complexes). But the most important function of metal ions is their participation in the biological reaction, as respiration, energy transfer, photosynthesis, nitrogen fixation. The bioinorganic species are often remarkably effective catalysts, known as metalloenzymes [18]. These compounds are enzyme proteins containing the metal ions bonded with the protein or the enzyme-bound nonprotein components. They are characterized by high reactivity and selectivity. Moreover, Sigel and Pyle [19] suggested that also ribozymes, i.e., RNA molecules with enzyme function may be considered as metalloenzymes because of the presence of functionally important metal ions (mostly divalent metal ions such as Mg2+) in their structure. This review will cover challenges in an application of artificial metalloenzymes as catalysts in non-natural compounds synthesis. Artificial metalloenzymes are the superior alternatives to native metalloenzymes and classical organocatalysts. In most cases, conditions required with enzymes are milder than those required with either homogeneous or heterogeneous catalysts. The discussion is organized based on their enantio- and regioselectivities, as well as catalytic activities and the majority of these examples were reported within the last few years. Moreover computational methods, which are helpful for further development of new artificial metalloenzyme catalyst systems and explanation of the reaction mechanism, are discussed.

2. Metalloenzymes – basic principle The selection of a metal for use in enzymatic catalysis results from the combination of its physicochemical properties such as redox potential and coordination chemistry, and its accessibility in the environment for biological systems [20]. Researchers have studied the properties, function and mechanism of natural metalloenzymes for many years [21–30]. The studies indicate that the reactivity of them depends on several factors,

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

such as: (i) tuning of their redox properties, (ii) substrate accessibility, (iii) Lewis acidity of their metallic centre [31]. The reactivity and selectivity of the enzymes can be modified by changing the donor/acceptor character of the ligands, controlling their geometry and arrangement around the metallic centre. These assumptions have contributed to the conduct of a number of studies in the recent years on the synthesis and characterization of artificial metalloenzymes. As was described by Arnold [32] using chemical knowledge and information about structure and mechanism the new non-natural enzymes could be discovered and synthesized. Besides, as was described in the literature, there is a possibility to evolution new enzymes. Results from directed laboratory evolution experiments indicate that the evolution of a new function is driven by mutations that have little effect on the native function but large effects on the promiscuous functions that serve as starting point. These mutations can reconfigure the active site in enzymes [31,33–38]. In comparison with other synthetic approaches, asymmetric catalysis is a smart strategy. A small amount of catalyst can produce large quantities. Enzymes have excellent selective recognition properties, so they usually provide the highest levels of selectivity. Artificial metalloenzymes also offer new opportunities to improve catalytic efficiency and selectivity [13]. For this purpose, both chemical modification of the first coordination sphere and mutation of the host protein (i.e., the reaction environment) can be used to optimize the performance of the artificial metalloenzyme. Although highly enantioselective artificial metalloenzymes have been reported for a variety of transformations, they often display lower activity than classical catalysts [39,40]. The new, metalloenzymes obtained in laboratory are interesting not only from the scientist point of view. By changing their properties researchers can create the compounds which enable to generate new reactive intermediates in the presence of reagents not found in the natural environment or find alternative routes to natural products. They are able to obtain highly selective enzymes for synthesis. And the most important, using natural derivatives, researchers have been able to introduce human-creating products into the biological system [41,42].

3

Fig. 2. Cupredoxin [CuII(biot-pr-dpea)(SCys)]+2 [48]. This figure was generated from coordinates deposited in the Protein Data Bank (5K67.pdb) and the MBT Protein Workshop application available from the Research Collaboratory for Structural Bioinformatics [50].

3. Artificial metalloenzymes with immobilized metals complexes Artificial metalloenzymes consist of synthetic metal catalysts and enzyme or protein scaffolds to achieve their goals as chiral catalysts by combining the reactivity of the former with the adaptability of the latter. The combination of inorganic/organometallic and biopolymer components providing materials with a threedimensional structure is mainly responsible for the enantioselectivity. Preparing a homogeneous transition metal catalyst involves combining a metal precursor with one or multiple labile ligands that can provide many binding sites. The ligands employed can range from monodentate species (e.g. amines, imines, pyridine, phosphine based ligands etc.) to complex, polydentate, high molecular weight structures such as tridentate aromatic Schiff bases, terpyridine, bidentate phosphines and phosphites ligands. Proteins, which contain a range of metal-binding N, O and S functional groups within three dimensional, chiral structures, have therefore attracted attention as scaffolds for formation via metal coordination. Most of approaches to link synthetic catalysts and protein/ peptide scaffolds can be broadly classified as involving coordinating binding of scaffold residues to metal atoms (coordination by donor groups from amino-acid residues and often also by water or other small molecule), non-covalent binding of metal complexes (weak chemical bond that does not involve an intimate sharing of electrons), or covalent modification using a functionalized metal

Fig. 3. Streptavidin-S112Y-K121E complexed with palladium-containing biotin ligand [49]. This figure was generated from coordinates deposited in the Protein Data Bank (5CSE.pdb) and the MBT Protein Workshop application available from the Research Collaboratory for Structural Bioinformatics [50].

complex, mostly by a chemical modification of scaffold residues [40,43–46]. Non-covalent insertion of metal complexes instead of the typical covalent conjugations has been extensively used to incorporate metal cofactors into scaffold proteins without the conjugation of

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

4

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

metal ligands to scaffold residue and modification of native metal cofactors. This approach eliminates the need for the chemical modification of scaffold residues while still allowing the use of various cofactors for artificial metalloenzymes formation [47]. This bioconjugation of metal complexes can be applicable to diverse proteins and metal complexes. The most studied approach to generate artificial metalloenzymes for an organic catalysis via non-covalent interactions involves binding biotin-substituted cofactors to avidin or streptavidin scaffolds [46]. The biotinstreptavidin technology represents a versatile tool to create artificial metalloenzymes and other supramolecular assemblies, due to (i) unique anchoring ability; (ii) chemical transformation properties of biotinylated compounds and (iii) precise modification of the surrounding host protein. The metalloenzymes for organic catalysis via non-covalent to streptavidin ensures rapid and essentially quantitative artificial metalloenzymes formation, and the ease with which biotin can be attached to a range of metal complexes. Cupredoxins provide a notable example of that interaction. These electron-transfers copper proteins have active sites containing a mononuclear Cu centre with an unusual trigonal monopyramidal structure (Type 1 Cu) and a single trigonal plane Cu– Scys bond, responsible for its unique physical properties (Fig. 2) [48]. Other example is an artificial Suzukiase in which a biotinylated monophosphine palladium complex was introduced within streptavidin (Fig. 3). The DFT analyses have shown that the Pdphosphine ligand is effectively ‘‘locked” into place by the steric environment of the Sav mutant [49]. Coordinating metals with proteins can enable artificial metalloenzymes formation. Unfortunately, many reactions are catalysed by metals with ligands not found in nature. For the preparation of an artificial metalloenzyme using this approach there are two basic requirements that have to be fulfilled [44,51–53]. The first one is that the enzyme must contain a single reactive amino acid residue. Other solution is the using of mutagenesis. However, this process itself requires extensive engineering for each desired amino acid and is limited to complexes that can be formed in the presence of protein. The second requirement is that the enzyme must contain a chiral cavity big enough to accommodate the metal moiety, reactants and the substrate. For example, using hydrolase enzymes containing serine or cysteine residues that can react selectively with suitable electrophiles, the modification of scaffold is not required. It should be pointed out that enzymes containing multiple active binding residues can also be used, but it is necessary to remove the extra binding sites prior to the covalent metal linkage. Example of the introduced functionality into proteins is a modification with a genetically encoded azide- or alkynebearing amino acid and reacting this protein with an appropriate reagent. This modification provides a simple introduction of metal catalysts into proteins with the broad scaffold scope of covalent modification also eliminating the constraints of naturally occurring anchor residues [54]. Other example is the creation of an artificial metalloenzyme, which involves grafting a new active site onto the dimmer interface of the protein LmrR by conjugation of a bidentate ligand capable of binding Cu(II) [39,55]. In these studies the covalent anchoring of Cu (II)-phenanthroline and Cu(II)-2,20 -bipyridine complexes to the protein proceeds via a genetically introduced cysteine residue.

4. Recent advances in synthesis with artificial metalloenzymes 4.1. Oxidation and hydroxylation of olefins and benzyl moieties One of many practical examples of enzymes as catalysts in organic chemistry concerns the enzymatic synthesis of chenodeoxycholic acid from cholic acid [56]. The reaction is catalysed by 12a-hydroxysteroid dehydrogenase catalysed reduction of

a-ketoglutarate. This oxidation occurs at the sterically most hindered site, impossible using chemical reagents or catalysts without applying protective group methodology. Continuation of these experiments is a biotransformation of chenodeoxycholic acid into 7-ketolithocholic acid by a novel 7a-specific NADP+-dependent hydroxysteroid dehydrogenase isolated from Clostridium difficile [57]. Cytochromes P450 and their mutants have been ideal examples of artificial metalloenzymes in which metal is coordinated with proteins. Cytochromes P450 enzymes in biological processes catalyse the addition of hydroxyl groups, arising from protons and the cleavage of dioxygen, to the wide variety of secondary metabolite and xenobiotic substrates. This enzyme is mainly a monooxygenase with haem group as the active site, which is activated by the reaction with molecular oxygen. According to the literature suggestion the active species in catalysis is FeIV = O complex with a porphyrin radical [58]. They also work as catalyst for aryl-aryl coupling, S- N-, and O-dealkylations, decarboxylation, oxidative cyclization, alcohol and aldehyde oxidation, sulphoxidation, nitrogen oxidation, epoxidation, decarbonylation, and nitration and so ones. This type of metalloenzymes are metalloporphyrins consisting of an iron porphyrin with cysteine acting as an axial ligand (completely conserved cysteine serving as an axial ligand to the haem iron) [59]. A few engineered proteins with mutations at the axial position have been characterized as mechanistic probes of P450 monooxygenase chemistry, but not all of them catalyse monooxygenation. A successful example is a mutation of cysteine to serine in P450BM3, which is highly activating especially for cyclopropanation but not for epoxidation of styrene [60]. Designed unique serine-haem ligated cytochrome P411 that catalyses efficient and selective carbene transfers from diazoesters to olefins in intact Escherichia coli cells. Because of the catalytic promiscuity of these P450s, new reactions have been observed. The triple mutant of P450pyr monooxygenase (P450pyrTM) was identified that catalyses the asymmetric epoxidations of para-substituted styrenes [61]. Similarly, P450BM3 mutants, V87I and V87F, were screened for new activity towards meclofenamic acid, a non-steroidal antiinflammatory drug, and oxidized products were identified as 30 OH-methyl-meclofenamic acid, 5-OH-meclofenamic acid and 40 OH-meclofenamic acid [62]. Novel and improved activity of P450BM3 towards chrysene and pyrene was obtained by screening a new library developed by random mutagenesis. Three different mutants, named M3, P2 and K4, showed higher affinity and coupling efficiency for both substrates with faster rates of product formation compared with the wild-type enzyme [63]. Carbonic anhydrases is another class of naturally occurring metalloenzymes in which the native Zn2+ has been replaced by other transition metals. The first examples include the preparation of Mn-containing metalloenzymes for enantioselective epoxidation of olefins [64]. Although the affinity of carbonic anhydrases for manganese is low, the epoxidation activity of Mn-carbonic anhydrase catalyst was higher than that of free manganese, so the observed epoxides are formed from the reaction of Mncarbonic anhydrase catalyst. The enantioselectivity in the epoxidation of styrenes exhibited by the metalloenzyme was comparable to or better than that of classical peroxidases. The utility of other Mn-enzymes has also been demonstrated by Oohora et al. [65]. In these studies myoglobin reconstituted with a Mn-porphycene cofactor catalyses benzylic oxygenation. Researchers have indicated that the artificial cofactor is located in the intrinsic haembinding site with weak ligation by His93. It was shown that the catalytic activity of myoglobin towards substrate hydroxylation can be improved only by the insertion of Mn-porphycene cofactor into apo-myoglobin. This reaction occurs via a rate-determining step that involves hydrogen-atom abstraction by Mn(O) species and a subsequent rebound hydroxylation process which is similar

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

to the reaction mechanism of cytochrome P450. Jing et al. [66] and Jing with Kazlauskas [67] have successfully replaced the active site zinc in carbonic anhydrases with rhodium complexes ([Rh(cod)2] BF4 and [Rh(acac)(CO)2]). Removal of these histidine residues by chemical modification and site-directed mutagenesis minimized the non-specific binding of rhodium to the surface. The resulting Rh-carbonic anhydrases metalloenzymes were applied in the regioselective hydroformylation of styrene [67] and the chemoselective hydrogenation of cis-stilbene [66]. Konieczny et al. [68] have prepared soluble in organic media polymer–enzyme conjugates. Replacement of the native copper by osmate led to the formation of a new organo-soluble metalloenzyme that is active in the dihydroxylation of alkenes. Optimizing the reaction conditions with laccase polymer–enzyme conjugates strongly indicated that osmate is in the active site, thereby affording product enantioselectivity that exceeds classical Sharpless catalysts. Zhang et al. [69] have synthesized a selected structure of maleimide-substituted manganese terpyridine cofactor. This metalloenzyme catalysed hydrocarbon oxygenation reaction (benzylic oxygenation, olefin epoxydation and ethereal O-R dealkylation) in the presence or either oxone or peracetic acid. The results indicated the impact of scaffold structure on the regio-, enantio- and chemoselectivity of Mn-terpyridine cofactor.

5

genation of the enone using catalyst formed from the supramolecular incorporation of a biotinylated piano-stool complex, [Cp⁄Ir (Biot-p-L)Cl] [80]. The artificial metalloenzyme was encapsulated within PMOXA-b-PDMS-bPMOXA and the resulting vesicles catalysed the cascade 1,4-addition reaction, followed by E1cB elimination, thereby leading to the release of umbelliferone. The asymmetric transfer hydrogenation of imines, has received less attention, the biocatalytic imine reduction to afford chiral amines in one step, has been scarcely developed. This effect is related to the very low stability of this type compounds especially after contact with an aqueous solution. Ward with co-workers [81] have utilised a based on biotinstreptavidin technology for the reduction of imine. This reaction leads preferentially to the formation of the S-enantiomer, whereas all asymmetric transfer hydrogenases investigated in this study yield preferentially the Renantiomer. In the case of the N-alkylated TsDPEN derivatives, the reaction proceeds through a different enantioselection mechanism: for a given aminosulphonamide ligand configuration the opposite enantiomers (amines or alcohols) are produced [71,73]. Gamenar and Domínguez [82] have proposed novel imine reductases enable the enantioselective reduction of imines to afford optically active amines. 4.3. Olefin metathesis

4.2. Hydrogenation Asymmetric transfer hydrogenation of various ketones and imines was recently accomplished with high yield and enantioselectivity by artificial metalloenzymes designed from the biotin– (strept)avidin system [70–73] Pordea et al. have performed genetic modifications of the host protein and finally used P64G-L124V double mutant of streptavidin in combination with the [g6-(pcymene)Ru(Biot-p-L)Cl] complex. This hydride system has increased of the enantioselectivity up to 98% ee (R) for the reduction of p-methylacetophenone [70]. Madern et al. have tested the transfer hydrogenase activity of the metallopapains on 2,2,2trifluoroacetophenone [74]. In that study as catalysts ruthenium and rhodium complexes contained a dipyridylamine ligand substituted at the central nitrogen atom by an alkyl chain of four or five carbons terminated by a maleimide were used. The length of the linker arm between the dipyridylamine chelate and the anchoring maleimide function did have a slight effect on the conversion rate and the enantioselectivity for the R-enantiomer was higher for the metal cofactors with the 5-carbon linker arm. The enantioselective transfer hydrogenation of several prochiral ketones has also been achieved by applying [6-(arene)Ru(biotinligand)Cl]  streptavidin which were evolved by chemogenetic optimization [75]. An artificial metalloenzyme, arylsulphonamide-bearing IrCp⁄ pianostool complexes, catalysed enantioselective transfer hydrogenation of the cyclic imine salsolidine with up to 70% ee [76]. Chevalley and Salmain [77] have demonstrated that b-lactoglobulin binds d6-transition metal piano stool complexes bearing long chain alkyl substituents to form the artificial metalloenzymes that catalyse enantioselective transfer hydrogenation of trifluoroacetophenone with up to 26% ee. Ward with co-workers [78] have presented the design and application of a dually anchored artificial metalloenzyme for the reduction of prochiral imines. It was shown that coordination of the catalyst precursor to a suitably positioned histidine residue has a significant impact on the catalyst’s performance, both in terms of activity and of selectivity. The artificial metalloenzymes [g5-(Biot-2)RhCl2]5  K121H and [g5-(Biot-2)RhCl2] 5  S112H have provided unique selectivity. The same group has incorporated achiral biotinylated rhodiumdiphosphine complexes into streptavidin yields artificial metalloenzymes for the hydrogenation of N-protected dehydroamino acids [79] and in detail studied hydro-

Bio-catalytic cross-metathesis, leading to stereoselective coupling reactions of alkynes as well as polymerisation reactions, states a particularly powerful method in modern chemistry. Several artificial metalloenzymes capable of cross-metathesis reaction were reported. Grubbs-Hoveyda type catalysts can be anchored in a protein by dative, supramolecular or covalent interactions [83,84], and catalysts proposed by Hilvert and Ward amenable to influence the activity and selectivity by genetically modifying the protein structure by mutagenesis methods [85]. In most cases the catalytic activity has not been improved compared to the metal complex alone, but the hybrid systems allow on formation nonnatural organic compounds. For example, Klein, Gebbing and coworkers [86] have incorporated Grubbs-type catalyst in the pocket around the original active site of the specific enzyme for olefin metathesis. Other examples of the Grubbs-Hoveyda type ruthenium catalysts with an N-heterocyclic carbene (NHC) as ancillary ligand have been presented by Sauer et al. [87]. Jaschek et al. [88] have demonstrated novel example for creating new non-natural metabolic pathways inside living cells. This is a vivo applicability of the streptavidin–biotin technology for creating artificial metalloenzymes biot-Ru–SAVperi that catalyses olefin metathesis (Fig. 4). Recently Denard et al. have demonstrated a cooperative catalysis involving an organometallic catalyst and a metalloenzyme [89]. This transformation combined a rutheniumcatalysed olefin cross-metathesis reaction with a cytochrome P450-catalysed epoxidation. The tandem one-pot reaction provided higher yields than would be obtainable using the corresponding two-step sequence. The continuation of the study results in much better yield of the desired product which was 1.5 times higher than the hypothetical yield of stepwise reactions [89,90]. Kourist and co-workers have also used the tandem onepot reaction. They have combined a cofactor-free decarboxylase with a ruthenium metathesis catalyst to produce high-value antioxidants from bio-based precursors [91]. The applicability of this methodology has been demonstrated by the synthesis of 4,40 -dihydroxystilbene in an overall yield of 90%. 4.4. Diels–Alder reactions Excellent endo-selectivities and enantioselectivities have been reported for the Diels–Alder reactions between cyclopentadiene

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

6

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

Fig. 4. Binding of the cofactor biot-Ru in crystal structure [88]. This figure was generated from coordinates deposited in the Protein Data Bank (5IRA.pdb) and the MBT Protein Workshop application available from the Research Collaboratory for Structural Bioinformatics [50].

and bidentate dienophiles [92,93]. Although the catalyst loading remains very high at this stage, such hybrid catalysts offer an attractive alternative to artificial metalloenzymes based on proteins as hosts. Gozin and Hilvert have tested a series of substituted thiophene dioxides as diene substrates for the antibody 1E9 [94]. It has been indicated that the antibody Diels–Alder cycloaddition reaction between tetrachlorothiophene dioxide and Nethylmaleimide proceeds via a transition state that looks very much like hexachloronorbornene derivative, which was used as haptene to generate the catalytic antibodies. Podtetenieff et al. have chosen Cu(II) as the metal, envisioning the newly designed metalloenzyme as a catalyst in the asymmetric Diels–Alder reaction of azachalcone and cyclopentadiene [95]. Experimental evidence clearly showed that the Cu(II) coordinatively bounds to the amino acids at the artificial binding site where asymmetric Diels–Alder reaction occurs. Bos et al. [39] have constructed and next used the artificial metalloenzyme which proved to be capable of catalysing Diels–Alder reaction with excellent enantioselectivities that is up to 97% ee. Based on the crystal structure of LmrR, positions 19 and 89 were selected for the covalent attachment of a Cu(II) complex (structure minimizing the chance that the metal complexes will interfere with each other). Interestingly, LmrR_M89C_2, which contains a conjugated 2,20 -bipyridine instead of a phenanthroline ligand, gave rise to 66% ee of the opposite, that is, the () enantiomer of the endo isomer of the Diels– Alder product. Hence, by judicious choice of the Cu(II) binding ligand, both enantiomers of the Diels–Alder product can be accessed (endo/exo).

4.5. Friedel–Crafts alkylation The Friedel–Crafts reaction is a powerful carbon–carbon bond formation reaction in organic synthesis, and their application to an enantioselective alkylation of indole nucleus is an ongoing interest in the synthesis of natural products and potential medicinal intermediates. Roelfes and co-workers [96] have reported the first catalytic asymmetric Friedel– Crafts alkylation reaction with olefins using water as the solvent and Cu-dmbpy/st-DNA as the catalyst. Employing catalyst for reaction of a,b-unsaturated 2acyl imidazoles with heteroaromatic nucleophiles Roelfes and coworkers haves achieved the final product with excellent enantioselectivity (up to 93%). In further studies they have presented a novel strategy for preparation of artificial metalloenzymes utilizing AMBER stop codon suppression method using an evolved mutant tRNA/aaRS pair from Methanococcus jannaschii for the in vivo incorporation of metalbinding unnatural amino acids [97,98]. The resulting artificial Cu-BpyAla-LmrR metalloenzymes catalysed the asymmetric Friedel–Crafts alkylation reactions with enantioselectivities with yield 83% ee. It was found that human telomeric Gquadruplex metalloenzyme (G4DNA) can serve as a direct chiral catalyst for the enantioselective Friedel–Crafts reaction. When a G4DNA metalloenzyme is derived from Cu2+ ions and G4DNA, the activity and the enantioselectivity of the Friedel–Crafts reaction are considerably enhanced. Furthermore, it was found that the absolute configuration and the enantioselectivity of the product are sensitive to the DNA sequence, and the loop sequence in the G4DNA metalloenzyme plays an important role in the chiral

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

expression. Other results of this group have shown that the Cuorganic catalyst supported by st-DNA can be an effective approach to achieving a chemically challenging reaction in water [99]. Moreover, it has been proposed that the DNA acts as a pseudophase. Wang et al. have found that human telomeric G4DNA can serve as a direct chiral catalyst for the enantioselective Friedel–Crafts reaction [100]. The researchers have also found that using CuG4DNA metalloenzymes the activity and the enantioselectivity of the Friedel–Crafts reaction are considerably enhanced. Furthermore, it has also shown that the absolute configuration of the product is sensitive to the DNA sequence, and the loop sequence in the G4DNA metalloenzyme plays an important role in the chiral expression. McNaughton and co-workers have used a gel-shift in vitro nucleic acid selection to identify a 72-nucleotide deoxyribozyme that catalyses a Friedel–Crafts reaction [101]. This deoxyribozyme functions well in the in cis-reaction, wherein the acyl imidazole moiety is tethered the 50 end of DNA and the indole is liked to a biotin moiety at position 5. When the reaction is run in trans the deoxyribozyme catalyses formation of the Friedel–Crafts product in 72% isolated yield.

7

that allows them to catalyse this non-natural reaction as well as any of the wild-type P450s. Arnold group has also applied versions of P450 that promote carbene insertions into N–H bonds and to develop a C–H amination reaction using sulphonyl azide substrates [107]. This general approach has been extended beyond P450s with the report of C– N bond-forming reactions promoted by wild-type of a non-haem iron(II)-dependent halogenase (SyrB2) in the presence of both azide and nitrite anions [108]. SyrB2 can bind azide and nitrate and catalyse the C–H nitration and azidation of un-activated substrates. Myoglobin contains a haem cofactor that can also promote carbene mediated transfer reactions. This enzyme has ability to promote the insertion of a-diazo-ester-derived carbenes into C@C double bonds and into N–H bonds with high catalytic efficiency, as well as with excellent diastereo- and enantioselectivity [109– 111]. This enzyme has ability to promote the insertion of adiazo-ester-derived carbenes into C@C double bonds and into N– H bonds with high catalytic efficiency, as well as with excellent diastereo- and enantioselectivity [112]. The representative reactions catalysed by metalloenzymes are presented in Fig. 5.

4.6. Transfer reactions 5. Modelling of artificial metalloenzymes The transition metal-catalysed insertion of carbenoid species into C@C, N–H, S–H, O–H and C–H bonds constitutes a powerful approach to the construction of new carbon–carbon and carbon– heteroatom bonds in organic chemistry. During the last years biocatalytic systems based on natural enzymes and other protein and DNA scaffolds have been investigated in the context of carbene transfer reactions. The studies of Giovani et al. have demonstrated that engineered P450 variants the bacterial cytochrome P450 CYP102A1 represent promising biocatalysts for the synthesis of aryl aldehydes and ketones through the oxidative deamination of alkyl azides under mild reaction conditions [102]. It has been shown that haemcontaining enzymes possess basal activity in this reaction and it exhibits a broad substrate scope along with high catalytic activity, excellent chemoselectivity as well as reactivity towards secondary alkyl azides to corresponding ketones. Giovani et al. [103] have also tested the ability of wild-type sperm whale myoglobin to promote the conversion of benzyl azide to benzaldehyde. Roelfes and co-workers have proposed DNA/cationic porphyrin hybrid catalyst for carbene-transfer reactions [104]. The catalytic reactions of enantioselective cyclopropanation of styrene derivatives and the corresponding cyclopropanation products were conducted in water and the results showed promising results. Coelho et al. [105] have presented the detailed studies on the cyclopropanation by using as catalyst mutants from P450BM3. The results clearly showed that the studied cyclopropanation is robust to both electron- and electron-withdrawing substitutions on styrene. The studied versions of P450 were also active on 1,1-disubstituted olefins, with chimeric P450 C2G9R1 forming cyclopropanes in 77% yield. The P450 s were only moderately active with t-butyl diazoacetate as substrate (<30% yield), forming the trans product with >87% selectivity. Variant 7-11D was a competent cyclopropanation catalyst displaying strong preference for the cis product. Also Heel et al. have presented the utility of P450BM3 (CYP102A1) as en efficient catalyst in non-natural reactions (carbene and nitrene transfer) [106]. This non-natural reaction is enabled by the ability of ethyl diazoacetate to react with haem to generate the reactive iron–carbenoid intermediate that mediates styrene cyclopropanation. It was shown that an equivalent mutation in the selected P450s was found to activate carbene transfer chemistry both in vitro and in vivo. Furthermore, serum albumins show a high affinity for metal porphyrins and provide a hydrophobic pocket

The deep biochemical knowledge in combination with organic synthesis experiences and application of advance computational methods provides a powerful set of tools for development of new artificial metalloenzyme catalyst systems. The success of the design of these composites is highly dependent on an atomic understanding of the recognition process between inorganic and biological entities [113]. Structure-based computational design could help to improved catalytic activity and enantioselectivity of metalloenzymes (Fig. 6) [114]. Because the mechanism of chemical reactions catalysed by metalloenzymes passes through several steps involving different chemically stable and unstable structures, i.e. intermediates, transition states and activation barriers, the calculation of the energy of different structures is taken into account. The relationship between energy barriers and reaction rates is given by Transition State Theory (TST) [115]. Although the theory was developed to describe reaction dynamics in the gas phase, it is extended to aqueous phase. Literature analysis indicates that transition state theory provides a good general framework for enzyme-catalysed reactions or behaviour of enzymes and is widely used by researchers [116]. There are many different computational methods that can be used to study enzyme catalysed reactions, and the choice of an appropriate method is an important consideration. There are methods for modelling the structure and dynamics of metalloenzymes, and the reactions which are catalysed by them are based on empirical functions, as empirical valence bond (EVB) method [117–120] or empirical force field (MM). Moreover, methods based on quantum mechanics (QM) model or semi-empirical hybrid quantum mechanical/molecular mechanical (QM/MM) model are proposed. The EVB method allows to calculate free energy profiles of chemical reactions with respectively low computational cost even for large systems and is used for modelling enzyme-catalysed reactions. Usefulness of EVB has been demonstrated to be Warshel and collaborators in i.e. catalytic reaction of Carboxypeptidase-A (CPA) (zinc metalloenzyme), and its mutants with general acid-general base mechanisms (GAGB-1 and GAGB-2) [117]. Åqvist and coworkers [121] have applied EVB approach to simulate of the keto-enol(ate) isomerization steps in differently adapted citrate syntheses with psychrophilic and mesophilic enzymes. Kumar et al. [122] based on valence bond method indicated correlation

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

8

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

CH2

1.

CH3

H 2/CO 1:1

O

RT 2 Mpa DEPC-H4/10R+H17F-[Rh]

O

+ 31%

13%

O

2.

OH

HCOONa pH 6.25 [h6-(p-cymene)Ru(Biot-p-L)Cl]

CH3

CH3

L124V-P64G

H3C

H3C 98% ee (R)

3. O

LmrR_M89C_2

N

CH3

* *

Cu(NO3) 2 , 3 mol %

+

O

CH3

N up to 98% ee

4.

OCH3

N

N

O

O H3CO

deoxyribozyme

N

+

N H

N CH3

CH3

OCH3 N H OCH3

72%

5. N2

+

O

O

CH3

Mb(H64V/V68A/H93A) 0.2 mol % cofactor: Mn(ppIX)

O CH3

O O O 20%

Fig. 5. Representative reactions catalysed by metalloenzymes: 1. regioselective hydroformylation of styrene [67], 2. hydrogenase based on the biotin–streptavidin technology [70], 3. Diels–Alder reaction [39], 4. Friedel–Crafts alkylation [101] and 5. carbene transfer catalyst [112].

for substrate epoxidation reactions catalysed by a range of haem and nonhaem iron(IV)-oxo oxidants (cytochromes P450) with the strength of the O–H bond in the iron-hydroxo complex. Literature analysis shows that this method is not often used by researchers in the current years. The application of this method was always supported by the fact that it is not a method that requires complex calculations, such as quantum methods. Because computer power has increased considerably over the last few years, it has contributed to the possibility of more advanced calculation methods, as methods described below based on quantum mechanics model. Hybrid QM/MM methods have advantage of the high accuracy of QM methods and the low computational cost of MM methods.

The main idea of the hybrid QM/MM approach is to partition the entire system into two regions. The small and most important part of the system involved in bond breaking/forming or electronic excited-state processes is described by a reliable but expensive QM method. The rest of the system, such as solvent molecules or surrounding amino acid residues of a protein, is described by a very fast classical MM force field [123]. The first application of this method for a redox-active enzyme mechanism was made for radical copper enzyme galactose oxidase (GOase) and a low molecular weight analogue by Rothlisberger et al. [124]. This method is widely described in the literature. Its usefulness in anaerobic hydroxylation of alkylaromatic compounds by ethylbenzene dehy-

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

Fig. 6. Artificial metalloenzyme by computational design [113]. This figure was generated from coordinates deposited in the Protein Data Bank (5BRV.pdb) and the MBT Protein Workshop application available from the Research Collaboratory for Structural Bioinformatics [50].

drogenase (EbDH) was presented by Szaleniec and co-workers [125]. EbDH is a molybdoenzyme belonging to subfamily II of the DMSO reductase family that catalyses the oxygen-independent, stereo-specific hydroxylation of ethylbenzene to (S)-1phenylethanol ((S)-1). Theoretical QM/MM modelling was used to elucidate the structure of the catalytically active form of the enzyme and to study the reaction mechanism and factors determining its high degree of enantioselectivity. These methods give accurate results in both geometry and reaction mechanism simulations for catalytic mechanism with several zinc-containing enzymes, such as metallo-b-lactamases, aminopeptidases and angiotensin I-converting enzyme (ACE, EC 3.4.15.1) [126]. Gleeson and co-workers [127] used QM/MM method to assess the catalytic activity of dimethylmalate lyase (DMML) with five different substrates (2R,3S)-dimethylmalate, (2R)-methylmalate, oxaloacetate, oxaloacetate with magnesium, 3,3-difluoro-oxaloacetate and Smalate. Siegbahn and co-workers [58] described the catalytic reaction of alkene oxidation with particular emphasis on competition between epoxidation and allylic hydroxylation and their optymalization with QM/MM method. As catalyst the cytochromes P450, namely the iron(IV)-oxo porphyrin cation radical oxidant were proposed [121]. The same metalloenzyme and CYP2C9 was used by Lonsdale et al. [128] in the modelling of aromatic oxidation reaction. Because Density functional theory (DFT) methods, such as B3LYP (based on QM/MM calculations) neglected the dispersion interaction, authors proposed, successfully, the empirical dispersion correction. Moreover researches suggested that these effects will be also important in modelling reactions catalysed by other enzymes. In work [128] authors showed the good correlations between the structural model and mechanism based on QM/MM calculations in description of the rate-limiting step in the electrophilic aromatic hydroxylation reaction by hydroperoxyflavin catalysed by phenol hydroxylase (PH) and para-hydroxybenzoate hydroxylase (PHBH). Moreover the results showed that the enzyme-catalysed reaction is adequately described by transition state theory. In work [129] authors compared molecular dynamics (MD) simulations and density functional theory (DFT) - QM and QM/MM models, in prediction of two possible metabolic routes (aromatic

9

carbon oxidation and O-demethylation) of dextromethorphan in one specific P450 isoform (2D6). QM/MM calculations demonstrated a crucial role of the protein in determining reactivity of dextromethorphan in P450 2D6, and (in contrast to MD simulations, docking and QM model calculations) explain the experimentally observed lack of aromatic hydroxylation. Baker and co-workers [130] described the method of computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction. This reaction is important in organic synthesis forming two carbon–carbon bonds and up to four new stereogenic centres in one step. The exemplary of these reaction is reaction between 4-carboxybenzyltrans-1,3-butadiene-1carbamate and N,N-dimethylacrylamide. Authors not only computationally designed an enzyme that catalyses reaction but also verified these calculations experimentally with good agreement. They used quantum mechanical (QM) calculations to predict the transition state and Rosetta methodology to design in silico enzyme models containing active sites with the desired properties. Another approach to find new efficient, highly selective metalloenzymes is using artificial neural networks (ANN). ANN, the socalled ‘‘black-box”, is simple and effective predictive instrument for solving non-linear problems. Such non-linear relationship is observed between i.e. catalyst’s structures and the experimentally determined enantioselectivities. Mazurek et al. [131] demonstrated the utility of ANN methods and established the relationship between the structures of 360 ligand–protein combinations acting as artificial metalloenzymes (consist of biotinylated rhodiumdiphosphine complexes incorporated in streptavidin mutants acting as host protein) and the experimentally determined enantiomeric excess of catalysed hydrogenation reactions for acetamidoacrylic acid. The input parameters of presented model were structural data of metalloenzymes and the output – enantiomeric excess, %ee. Evidence that ANN predicted correctly enantioselectivity was presented also by Miller and co-workers for oxidations reactions with CYP2C19. The optimized geometries and partial atomic charges for CYP2C19 substrates were used to generate the conformation-independent chirality codes (CICC) for molecules as the input parameters, while catalytic parameters for enzymatic reactions as dependent output parameters [132]. Because, there is a great interest in the catalysis with the metalloenzyme the specific databases are proposed to help in prediction of the ability of using these catalysts in chemical reaction. These databases are very helpful, for example, to exclude certain enzymes as potential catalysts, and to focus on the calculation on those that have the most potential uses. Andreini and co-workers [133], and Almonacid and Babbitt [134] compared in detail the available databases focusing on metals in biology. This could help other authors choose the right base for their research work. An example of such a base is The Metal MACiE (Mechanism, Annotation and Classification in Enzymes) database [135]. It is the result of a collaborative project among three institutes: the Magnetic Resonance Center (University of Florence), the European Bioinformatics Institute and the Unilever Center (University of Cambridge). This database contains information on the properties and roles of metal ions in the catalytic mechanisms of metalloenzymes and it is used by researchers [132,136–139]. Also well known Protein Data Bank (PDB) [140] was extended to MetalPDB database [141], which takes into account metal–biomacromolecule interactions by supplementing the detailed analysis of metal coordination. Based on the different databases interesting information for researchers could be concluded. For example Andreini and Bertini [136] from the analysis of the PDB, PDBSprotEC and Metal-MACiE databases estimated that 10% of the chemical reactions catalysed by enzymes involve at least one catalytic mechanism that requires zinc to occur. This Protein Data Bank is currently widely used for description of metal-protein compounds [142–145].

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

10

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

6. Conclusions The review covers the latest developments in application of metalloenzymes as catalysts in non-natural compounds synthesis. Analysis of the latest literature in this field indicates that there are still new opportunities for application of metalloenzymes in chemical synthesis. The new reaction systems are still under development. In these searches, the modelling is very useful to predict the new artificial metalloenzyme catalyst systems and explanation of the reaction mechanism. The application of artificial metalloenzyme is an excellent alternative to the commonly used catalysts in non-natural compounds synthesis because of their high enantioand regioselectivities.

Acknowledgments This research was supported with 03/32/DS-PB/0700 and 03/32/DS-PB/0701 grants. Authors are grateful to Erasmus+ the European Union programme. We thank the Staff Mobility for Training Programme for training opportunities in Centre for Natural Resources and the Environment in Lisbon, Portugal and fruitful discussions during our stay.

References [1] I. Bertini, H.B. Gray, E.I. Stiefel, J.S. Valentine, Biological Inorganic Chemistry, University Science Books, Sausalito, 2006. [2] A.F.A. Peacock, Incorporating metals into de novo proteins, Curr. Opin. Chem. Biol. 17 (2013) 934–939. [3] Y.Z. Hamada, Metal ions role in biological systems, Electron. J. Biol. S2 (2010) 1. [4] K.L. Haas, K.J. Franz, Application of metal coordination chemistry to explore and manipulate cell biology, Chem. Rev. 109 (2009) 4921–4960. [5] C.J. Chang, C. He, Using chemistry to study and control metals in biology, Curr. Opin. Chem. Biol. 17 (2013) 127–128. [6] R.A. Festa, D.J. Thiele, Copper: an essential metal in biology, Curr. Biol. 21 (2011) R877–R883. [7] B.J. Herring, A.L. Logsdon, J.E. Lockard, B.M. Miller, H. Kim, E.A. Calderon, J.B. Vincent, M.M. Bailey, Long-term exposure to [Cr3O(O2CCH2CH3)6(H2O)3]+ in Wistar rats fed normal or high-fat diets does not alter glucose metabolism, Biol. Trace Elem. Res. 151 (2013) 406–414. [8] A.M. Standeven, K.E. Wetterhahn, Chromium(VI) toxicity: uptake, reduction, and DNA damage, Int. J. Toxicol. 8 (1989) 1275–1283. [9] C.E. Housecroft, A.G. Sharpe, Inorganic Chemistry, second ed., Pearson Education Limited, Edinburgh, 2005. [10] C.R. Lee, J.S. Yoon, Y.-W. Suh, J.-W. Choi, J.-M. Ha, D.J. Suh, Y.-K. Park, Catalytic roles of metals and supports on hydrodeoxygenation of lignin monomer guaiacol, Catal. Commun. 17 (2012) 54–58. [11] S.J.A. Pope, B.J. Coe, S. Faulkner, E.V. Bichenkova, X. Yu, K.T. Douglas, Selfassembly of heterobimetallic df hybrid complexes: sensitization of lanthanide luminescence by d-block metal-to-ligand charge-transfer excited states, J. Am. Chem. Soc. 126 (2004) 9490–9491. [12] G.F. Swiegers, Mechanical Catalysis: Methods of Enzymatic, Homogeneous, and Heterogeneous Catalysis, John Wiley & Sons Inc, 2008. [13] J.C. Lewis, Artificial metalloenzymes and metallopeptide catalysts for organic synthesis, ACS Catal. 3 (2013) 2954–2975. [14] S. Miyashita, C. Audretsch, Z. Nagy, R.M. Füchslin, R. Pfeifer, Mechanical catalysis on the centimetre scale, J. R. Soc. Interface 12 (2015) 1271–1278. [15] D.A. Bruce, Mechanical catalysis: methods of enzymatic, homogeneous, and heterogeneous catalysis, J. Am. Chem. Soc. 131 (2009) 14597. [16] C. Orvig, M.J. Abrams, Medicinal inorganic chemistry: introduction, Chem. Rev. 99 (1999) 2201–2203. [17] S.F.A. Kettle, Physical Inorganic Chemistry. A Coordination Chemistry Approach, Oxford University Press, 1996. [18] M. Hoppert, Metalloenzymes, in: J. Reitner, V. Thiel (Eds.), Encyclopedia of Geobiology, Encyclopedia of Earth Sciences Series, Springer, Amsterdam, 2011, pp. 558–563. [19] R.K.O. Sigel, A.M. Pyle, Alternative roles for metal ions in enzyme catalysis and the implications for ribozyme chemistry, Chem. Rev. 107 (2007) 97–113. [20] C. Andreini, I. Bertini, G. Cavallaro, G.L. Holliday, J.M. Thornton, Metal ions in biological catalysis: from enzyme databases to general principles, J. Biol. Inorg. Chem. 13 (2008) 1205–1218. [21] D.D. Ulmer, B.L. Vallee, Structure and function of metalloenzymes, in: R. Dessy, J. Dillard, L. Taylor (Eds.), Bioinorganic Chemistry, ACS Publications, 1971, pp. 187–218. [22] K. Degtyarenko, Bioinorganic motifs: towards functional classification of metalloproteins, Bioinformatics 16 (2000) 851–864.

[23] M. Shoji, H. Isobe, Y. Takano, Y. Kitagawa, S. Yamanaka, M. Okumura, K. Yamaguchi, Theory of chemical bonds in metalloenzymes. IX. Theoretical study on the active site of the ribonucleotide reductase and the related species, Int. J. Quantum Chem. 107 (2007) 3250–3265. [24] M. Shoji, H. Isobe, T. Saito, Y. Kitagawa, S. Yamanaka, T. Kawakami, M. Okumura, K. Yamaguchi, Theory of chemical bonds in metalloenzymes XI: Full geometry optimization and vibration analysis of porphyrin iron-oxo species, Int. J. Quantum Chem. 108 (2008) 2950–2965. [25] M. Shoji, H. Isobe, T. Saito, H. Yabushita, K. Koizumi, Y. Kitagawa, S. Yamanaka, T. Kawakami, M. Okumura, M. Hagiwara, K. Yamaguchi, Theory of chemical bonds in metalloenzymes. VII. Hybrid-density functional theory studies on the electronic structures of P450, Int. J. Quantum Chem. 108 (2008) 631–650. [26] R.D. Kersten, P.C. Dorrestein, Metalloenzymes: natural product nitrosation, Nat. Chem. Biol. 6 (2010) 636–637. [27] K. Yamaguchi, M. Shoji, T. Saito, H. Isobe, S. Nishihara, K. Koizumi, S. Yamada, T. Kawakami, Y. Kitagawa, S. Yamanaka, M. Okumura, Theory of chemical bonds in metalloenzymes. XV. Local singlet and triplet diradical mechanisms for radical coupling reactions in the oxygen evolution complex, Int. J. Quantum Chem. 110 (2010) 3101–3128. [28] T. Saito, M. Shoji, K. Kanda, H. Isobe, S. Yamanaka, Y. Kitagawa, S. Yamada, T. Kawakami, M. Okumura, K. Yamaguchi, Theory of chemical bonds in metalloenzymes. XVII. Symmetry breaking in manganese cluster structures and chameleonic mechanisms for the OO bond formation of water splitting reaction, Int. J. Quantum Chem. 112 (2012) 121–135. [29] Y. Yu, C. Cui, J. Wang, Y. Lu, Biosynthetic approach to modeling and understanding metalloproteins using unnatural amino acids, Sci. China Chem. 60 (2017) 188–200. [30] M.R. Nechay, C.E. Valdez, A.N. Alexandrova, Computational treatment of metalloproteins, J. Phys. Chem. B 119 (2015) 5945–5956. [31] M. Hoarau, C. Hureau, E. Gras, P. Faller, Coordination complexes and biomolecules: a wise wedding for catalysis upgrade, Coord. Chem. Rev. 308 (2016) 445–459. [32] F.H. Arnold, The nature of chemical innovation: new enzymes by evolution, Q. Rev. Biophys. 48 (2015) 404–410. [33] A. Aharoni, L. Gaidukov, O. Khersonsky, S. McQ Gould, C. Roodveldt, D.S. Tawfik, The ‘evolvability’ of promiscuous protein functions, Nat. Genet. 37 (2005) 73–76. [34] M.E. Glasner, J.A. Gerlt, P.C. Babbitt, Evolution of enzyme superfamilies, Curr. Opin. Chem. Biol. 10 (2006) 492–497. [35] F. Baier, J.N. Copp, N. Tokuriki, Evolution of enzyme superfamilies: comprehensive exploration of sequence–function relationships, Biochemistry 55 (2016) 6375–6388. [36] M.E. Glasner, J.A. Gerlt, P.C. Babbitt, Mechanisms of protein evolution and their application to protein engineering, in: E.A. Toone (Ed.), Advances in enzymology and related areas of molecular biology, Protein Evolution, vol. 75, Wiley & Sons, Hoboken, NJ, USA, 2006, pp. 193–239. [37] S.M. Cuesta, S.A. Rahman, N. Furnham, J.M. Thornton, The classification and evolution of enzyme function, Biophys. J. 109 (2015) 1082–1086. [38] S.D. Brown, P.C. Babbitt, New insights about enzyme evolution from large scale studies of sequence and structure relationships, J. Biol. Chem. 289 (2014) 30221–30228. [39] J. Bos, F. Fusetti, A.J.M. Driessen, G. Roelfes, Enantioselective artificial metalloenzymes by creation of a novel active site at the protein dimer interface, Angew. Chem. Int. Ed. 51 (2012) 7472–7475. [40] J. Bos, G. Roelfes, Artificial metalloenzymes for enantioselective catalysis, Curr. Opin. Chem. Biol. 19 (2014) 135–143. [41] H.M. Key, P. Dydio, D.S. Clark, J.F. Hartwig, Abiological catalysis by artificial haem proteins containing noble metals in place of iron, Nature 534 (2016) 534–537. [42] P. Dydio, H.M. Key, A. Nazarenko, J.Y.E. Rha, V. Seyedkazemi, D.S. Clark, J.F. Hartwig, An artificial metalloenzyme with the kinetics of native enzymes, Science 354 (2016) 102–106. [43] M. Creus, T.R. Ward, Designed evolution of artificial metalloenzymes: protein catalysts made to order, Org. Biomol. Chem. 5 (2007) 1835–1844. [44] J.C. Lewis, Artificial metalloenzymes and metallopeptide catalysts for organic synthesis, ACS Catal. 3 (12) (2013) 2954–2975. [45] Y. Lu, N. Yeung, N. Sieracki, N.M. Marshall, Review article design of functional metalloproteins, Nature 460 (2009) 855–862. [46] T. Heinisch, T.R. Ward, Artificial metalloenzymes based on the biotinstreptavidin technology: challenges and opportunities, Acc. Chem. Res. 49 (2016) 1711–1721. [47] T. Ueno, T. Koshiyama, S. Abe, N. Yokoi, M. Ohashi, H. Nakajima, Y. Watanabe, Design of artificial metalloenzymes using non-covalent insertion of a metal complex into a protein scaffold, J. Organomet. Chem. 692 (2007) 142–147. [48] S.I. Mann, T. Heinisch, A.C. Weitz, M.P. Hendrich, T.R. Ward, A.S. Borovik, Modular artificial cupredoxins, J. Am. Chem. Soc. 138 (2016) 9073–9076. [49] A. Chattergee, H. Mallin, J. Klehr, J. Vallapurackal, A.D. Finke, L. Vera, M. Marsh, T.R. Ward, An enantioselective artificial suzukiase based on the biotinstreptavidin technology, Chem. Sci. 7 (2016) 673–677. [50] J.L. Moreland, A. Gramada, O.V. Buzko, Q. Zhang, P.E. Bourne, The Molecular Biology Toolkit (MBT): a modular platform for developing molecular visualization applications, BMC Bioinf. 6 (2005) 21. [51] C.J. Lewis, Metallopeptide catalysts and artificial metalloenzymes containing unnatural amino acids, Curr. Opin. Chem. Biol. 25 (2015) 27–35.

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx [52] T. Matsuo, S. Hirota, Artificial enzymes with protein scaffolds: Structural design and modification, Bioorg. Med. Chem. 22 (2014) 5638–5656. [53] T.K. Hyster, T.R. Ward, Genetic optimization of metalloenzymes: enhancing enzymes for non-natural reactions, Angew. Chem. 55 (2016) 7344–7357. [54] H. Yang, P. Srivastava, C. Zhang, J.C.A. Lewis, General method for artificial metalloenzyme formation through strain-promoted azide-alkyne cycloaddition, ChemBioChem 15 (2014) 223–227. [55] J. Bos, A. García-Herraiz, G. Roelfes, An enantioselective artificial metallohydratase, Chem. Sci. 4 (2013) 3578–3582. [56] G. Carrea, R. Bovara, R. Longhi, S. Riva, Preparation of 12ketochenodeoxycholic acid from cholic acid using co-immobilized 12ahydroxysteroid dehydrogenase and glutamate dehydrogenase with NADP+ cycling at high efficiency, Enzyme Microb. Technol. 7 (1985) 597–600. [57] D. Bakonyi, W. Hummel, Cloning, expression, and biochemical characterization of a novel NADP+-dependent 7a-hydroxysteroid dehydrogenase from Clostridium difficile and its application for the oxidation of bile acids, Enzyme Microb. Technol. 99 (2017) 16–24. [58] M.R.A. Blomberg, T. Borowski, F. Himo, R.-Z. Liao, P.E.M. Siegbahn, Quantum chemical studies of mechanisms for metalloenzymes, Chem. Rev. 114 (2014) 3601–3658. [59] S.M. Barry, J.A. Kers, E.G. Johnson, L. Song, P.R. Aston, B. Patel, S.B. Krasnoff, B. R. Crane, D.M. Gibson, R. Loria, G.L. Challis, Cytochrome P450–catalyzed Ltryptophan nitration in thaxtomin phytotoxin biosynthesis, Nat. Chem. Biol. 8 (2012) 814–816. [60] P.S. Coelho, Z.J. Wang, M.E. Ener, S.A. Baril, A. Kannan, F.H. Arnold, E.M. Brustad, A Serine-substituted P450 catalyzes highly efficient carbene transfer to olefins In Vivo, Nat. Chem. Biol. 9 (2013) 485–487. [61] A. Li, J. Liu, S.Q. Pham, Z. Li, Engineered P450pyr monooxygenase for asymmetric epoxidation of alkenes with unique and high enantioselectivity, Chem. Commun. (Camb.) 49 (2013) 11572–11574. [62] H. Venkataraman, M.C. Verkade-Vreeker, L. Capoferri, D.P. Geerke, N.P. Vermeulen, J.N. Commandeur, Application of engineered cytochrome P450 mutants as biocatalysts for the synthesis of benzylic and aromatic metabolites of fenamic acid NSAIDs, Bioorg. Med. Chem. 22 (2014) 5613– 5620. [63] A. Sideri, A. Goyal, G. Di Nardo, G.E. Tsotsou, G. Gilardi, Hydroxylation of nonsubstituted polycyclic aromatic hydrocarbons by cytochrome P450 BM3 engineered by directed evolution, J. Inorg. Biochem. 120 (2013) 1–7. [64] A. Fernández-Gacio, A. Codina, J. Fastrez, O. Riant, P. Soumillion, Transforming carbonic anhydrase into epoxide synthase by metal exchange, ChemBioChem 7 (2006) 1013–1016. [65] K. Oohora, Y. Kihira, E. Mizohata, T. Inoue, T. Hayashi, C(sp3)H bond hydroxylation catalyzed by myoglobin reconstituted with manganese porphycene, J. Am. Chem. Soc. 135 (2013) 17282–17285. [66] Q. Jing, K. Okrasa, R.J. Kazlauskas, Stereoselective hydrogenation of olefins using rhodium-substituted carbonic anhydrase – a new reductase, Chem. Eur. J. 15 (2009) 1370–1376. [67] Q. Jing, R.J. Kazlauskas, Regioselective hydroformylation of styrene using rhodium-substituted carbonic anhydrase, ChemCatChem 2 (2010) 953–957. [68] S. Konieczny, M. Leurs, J.C. Tiller, Polymer enzyme conjugates as chiral ligands for sharpless dihydroxylation of alkenes in organic solvents, ChemBioChem 16 (2015) 83–90. [69] C. Zhang, P. Srivastava, K. Ellis-Guardiola, J.C. Lewis, Manganese terpyridine artificial metalloenzymes for benzylic oxygenation and olefin epoxidation, Tetrahedron 70 (2014) 4245–4249. [70] A. Pordea, M. Creus, C. Letondor, A. Ivanova, T.R. Ward, Improving the enantioselectivity of artificial transfer hydrogenases based on the biotin– streptavidin technology by combinations of point mutations, Inorg. Chim. Acta 363 (2010) 601–604. [71] M. Durrenberger, T. Heinisch, Y.M. Wilson, T. Rossel, E. Nogueira, L. Knorr, A. Mutschler, K. Kersten, M.J. Zimbron, J. Pierron, T. Schirmer, T.R. Ward, Artificial transfer hydrogenases for the enantioselective reduction of cyclic imines, Angew. Chem. Int. Ed. 50 (2011) 3026–32029. [72] M.V. Cherrier, S. Engilberge, P. Amara, A. Chevalley, M. Salmain, J.C. Fontecilla-Camps, Structural basis for enantioselectivity in the transfer hydrogenation of a ketone catalyzed by an artificial metalloenzyme, Eur. J. Inorg. Chem. 2013 (2013) 3596–3600. [73] J.E.D. Martins, G.J. Clarkson, M. Wills, Ru(II) complexes of N-alkylated TsDPEN ligands in asymmetric transfer hydrogenation of ketones and imines, Org. Lett. 11 (2009) 847–850. [74] N. Madern, B. Talbi, M. Salmain, Aqueous phase transfer hydrogenation of aryl ketones catalysed by achiral ruthenium(II) and rhodium(III) complexes and their papain conjugates, Appl. Organomet. Chem. 27 (2013) 6–12. [75] T.K. Hyster, L. Knörr, T.R. Ward, T. Rovis, Biotinylated Rh(III) complex in engineered streptavidin for accelerated asymmetric C-H activation, Science 338 (2012) 500–506. [76] F.W. Monnard, E.S. Nogueira, T. Heinisch, T. Schirmer, T.R. Ward, Human carbonic anhydrase II as host protein for the creation of artificial metalloenzymes: the asymmetric transfer hydrogenation of imines, Chem. Sci. 4 (2013) 3269–3274. [77] A. Chevalley, M. Salmain, Enantioselective transfer hydrogenation of ketone catalysed by artificial metalloenzymes derived from bovine b-lactoglobulin, Chem. Commun. 48 (2012) 11984–11986. [78] J.M. Zimbron, T. Heinisch, M. Schmid, D. Hamels, E.S. Nogueira, T. Schirmer, T. R. Ward, A dual anchoring strategy for the localization and activation of

[79]

[80]

[81]

[82]

[83]

[84] [85] [86]

[87] [88]

[89]

[90]

[91]

[92] [93] [94] [95]

[96]

[97]

[98]

[99]

[100]

[101] [102] [103]

[104]

[105]

[106]

[107]

11

artificial metalloenzymes based on the biotin–streptavidin technology, J. Am. Chem. Soc. 135 (2013) 5384–5390. J. Collot, J. Gradinaru, N. Humbert, M. Skander, A. Zocchi, T.R. Ward, Artificial metalloenzymes for enantioselective catalysis based on biotinavidin, J. Am. Chem. Soc. 125 (2003) 9030–9031. T. Heinisch, K. Langowska, P. Tanner, J. Reymond, W. Meier, C. Palivan, T.R. Ward, Fluorescence-based assay for the optimization of the activity of artificial transfer hydrogenase within a biocompatible compartment, ChemCatChem 5 (2013) 720–723. F. Schwizer, V. Koehler, M. Dürrenberger, L. Knörr, T.R. Ward, Genetic optimization of the catalytic efficiency of artificial imine reductases based on biotin–streptavidin technology, ACS Catal. 3 (2013) 1752–1760. D. Gamenara, P. Domínguez de María, Enantioselective imine reduction catalyzed by imine reductases and artificial metalloenzymes, Org. Biomol. Chem. 12 (2014) 2989–2992. C. Lo, M.R. Ringenberg, D. Gnandt, Y. Wilson, T.R. Ward, Artificial metalloenzymes for olefin metathesis based on the biotin-(strept)avidin technology, Chem. Commun. 47 (2011) 12065–12067. C. Mayer, D.G. Gillingham, T.R. Ward, D. Hilvert, An artificial metalloenzyme for olefin metathesis, Chem. Commun. 47 (2011) 12068–12070. T. Heinisch, T.R. Ward, Latest developments in metalloenzyme design and repurposing, Eur. J. Inorg. Chem. 2015 (2015) 3406–3418. M. Basauri-Molina, D.G.A. Verhoeven, J.A. Van Schaik, H. Kleijn, R.J.M. Klein, Gebbink, Ring-closing and cross-metathesis with artificial metalloenzymes created by covalent active site-directed hybridization of a lipase, Chem. Eur. J. 21 (2015) 15676–15685. D.F. Sauer, S. Gotzen, J. Okuda, Metatheases: artificial metalloproteins for olefin metathesis, Org. Biomol. Chem. 14 (2016) 9174–9183. M. Jeschek, R. Reuter, T. Heinisch, C. Trindler, J. Klehr, S. Panke, T.R. Ward, Directed evolution of artificial metalloenzymes for in vivo metathesis, Nature 537 (2016) 661–665. C.A. Denard, H. Huang, M.J. Bartlett, L. Lu, Y. Tan, H. Zhao, J.F. Hartwig, Cooperative tandem catalysis by an organometallic complex and a metalloenzyme, Angew. Chem. Int. Ed. 53 (2013) 465–469. C.A. Denard, M.J. Bartlett, Y. Wang, L. Lu, J.F. Hartwig, H. Zhao, Development of a one-pot tandem reaction combining ruthenium-catalyzed alkene metathesis and enantioselective enzymatic oxidation to produce aryl epoxides, ACS Catal. 5 (2015) 3817–3822. G.Á. Baraibar, D. Reichert, C. Mügge, S. Seger, H. Gröger, R. Kourist, A one-pot cascade reaction combining an encapsulated decarboxylase with a metathesis catalyst for the synthesis of bio-based antioxidants, Angew. Chem. Int. Ed. 55 (2016) 14823–14827. G. Roelfes, B.L. Feringa, DNA-based asymmetric catalysis, Angew. Chem. Int. Ed. 44 (2005) 3230–3232. G. Roelfes, A.J. Boersma, B.L. Feringa, Highly enantioselective DNA-based catalysis, Chem. Commun. 6 (2006) 635–637. Y. Gozin, D. Hilvert, Steric and electronic effects on an antibody-catalyzed Diels-Alder reaction, Helv. Chim. Acta 85 (2002) 4328–4336. J. Podtetenieff, A. Taglieber, E. Bill, E.J. Reijerse, M.T. Reetz, An artificial metalloenzyme: creation of a designed copper binding site in a thermostable protein, Angew. Chem. Int. Ed. 49 (2010) 5151–5155. A.J. Boersma, B.L. Feringa, G. Roelfes, Enantioselective Friedel-Crafts reactions in water using a DNA based catalyst, Angew. Chem. Int. Ed. 48 (2009) 3346– 3348. I. Drienovska, A. Rioz-Martinez, A. Draksharapu, G. Roelfes, Novel artificial metalloenzymes by in vivo incorporation of metal-binding unnatural amino acids, Chem. Sci. 6 (2015) 770–776. I. Drienovska, G. Roelfes, Artificial metalloenzymes for asymmetric catalysis by creation of novel active sites in protein and DNA scaffolds, Israel J. Chem. 55 (2015) 21–31. A. García-Fernández, R.P. Megens, L. Villarino, G. Roelfes, DNA-accelerated copper catalysis of Friedel-Crafts conjugate addition/enantioselective protonation reactions in water, J. Am. Chem. Soc. 138 (2016) 16308–16314. C. Wang, Y. Li, G. Jia, Y. Liu, S. Lu, C. Li, Enantioselective Friedel-Crafts reactions in water catalyzed by a human telomeric G-quadruplex DNA metalloenzyme, Chem. Commun. 48 (2012) 6232–6234. U. Mohan, R. Buraia, B.R. McNaughton, In vitro evolution of a Friedel-Crafts deoxyribozyme, Org. Biomol. Chem. 11 (2013) 2241–2244. S. Giovani, H. Alwaseem, R. Fasan, Aldehyde and ketone synthesis by P450catalyzed oxidative deamination of alkyl azides, ChemCatChem 8 (2016) 1–6. M.S. Giovani, R. Singh, R. Fasan, Efficient conversion of primary azides to aldehydes catalyzed by active site variants of myoglobin, Chem. Sci. 7 (2016) 234–239. A. Rioz-Martínez, J. Oelerich, N. Ségaud, G. Roelfes, DNA-accelerated catalysis of carbene transfer reactions by a DNA/cationic iron porphyrin hybrid, Angew. Chem. Int. Ed. 55 (2016) 14136–14140. P.S. Coelho, E.M. Brustad, A. Kannan, F.H. Arnold, Olefin cyclopropanation via carbene transfer catalyzed by engineered Cytochrome P450 Enzymes, Science 339 (2013) 307–310. T. Heel, J.A. McIntosh, S.C. Dodani, J.T. Meyerowitz, F.H. Arnold, Non-natural olefin cyclopropanation catalyzed by diverse Cytochrome P450s and other hemoproteins, ChemBioChem 15 (2014) 1–8. Z.J. Wang, N.E. Peck, H. Renata, F.H. Arnold, Cytochrome P450-catalysed insertion of carbenoids into N-H bonds, Chem. Sci. 5 (2014) 598–601.

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012

12

K. Wieszczycka, K. Staszak / Coordination Chemistry Reviews xxx (2017) xxx–xxx

[108] M.L. Matthews, W. Chang, A.P. Layne, L.A. Miles, C. Krebs, J.M. Bollinger, Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase, Nat. Chem. Biol. 10 (2014) 209–215. [109] R. Singh, J.N. Kolev, P.A. Sutera, R. Fasan, Enzymatic C(sp3)-H amination: P450-catalyzed conversion of carbonazidates into oxazolidinones, ACS Catal. 5 (2015) 1685–1691. [110] G. Sreenilayam, R. Fasan, Myoglobin-catalyzed intermolecular carbene N-H insertion with arylamine substrates, Chem. Commun. (Camb.) 51 (2015) 1532–1534. [111] V. Tyagi, G. Sreenilayam, P. Bajaj, A. Tinoco, R. Fasan, Biocatalytic synthesis of allylic and allenyl sulfides via a myoglobin-catalyzed Doyle-Kirmse reaction, Angew. Chem. Int. Ed. Engl. 55 (2016) 13562–13566. [112] R. Fasan, G. Sreenilayam, E. Moore, V. Steck, Metal substitution modulates the reactivity and extends the reaction scope of myoglobin carbene transfer catalysts, Adv. Synth. Catal. 359 (2017) 2076–2089. [113] V.M. Robles, E. Ortega-Carrasco, E.G. Fuentes, A. Lledós, J.-D. Maréchal, What can molecular modelling bring to the design of artificial inorganic cofactors?, Faraday Discuss 148 (2011) 137–159. [114] T. Heinisch, M. Pellizzoni, M. Dürrenberger, C.E. Tinberg, V. Köhler, J. Klehr, D. Häussinger, D. Baker, T.R. Ward, Improving the catalytic performance of an artificial metalloenzyme by computational, J. Am. Chem. Soc. 137 (2015) 10414–10419. [115] A.S.J.L. Bachmeier, Metalloenzymes as Inspirational Electrocatalysts for Artificial Photosynthesis, Springer, 2017, From Mechanism to Model Device. [116] R. Lonsdale, J.N. Harvey, A.J. Mulholland, A practical guide to modelling enzyme-catalysed reactions, Chem. Soc. Rev. 41 (2012) 3025–3038. [117] E. Chudyk, Empirical valence bond methods, in: G.C.K. Roberts (Ed.), Encyclopedia of Biophysics, Springer, 2013, pp. 663–664. [118] A.V. Kilshtain, A. Warshel, On the origin of the catalytic power of carboxypeptidase a and other metalloenzymes, Proteins 77 (2009) 536–550. [119] S.C.L. Kamerlin, A. Warshel, The EVB as a quantitative tool for formulating simulations and analyzing biological and chemical reactions, Faraday Discuss. 145 (2010) 71–106. [120] S.C.L. Kamerlin, A. Warshel, The empirical valence bond model: theory and applications, WIREs Comput. Mol. Sci. 1 (2011) 30–45. [121] S. Bjelic, B.O. Brandsdal, J. Åqvist, Cold Adaptation of enzyme reaction rates, Biochemistry 47 (2008) 10049–10057. [122] D. Kumar, B. Karamzadeh, G.N. Sastry, S.P. de Visser, What factors influence the rate constant of substrate epoxidation by compound I of cytochrome P450 and analogous iron(IV)-oxo oxidants?, J Am. Chem. Soc. 132 (2010) 7656–7667. [123] L.W. Chung, H. Hirao, X. Li, K. Morokuma, The ONIOM method: its foundation and applications to metalloenzymes and photobiology, WIREs Comput. Mol. Sci. 2 (2012) 327–350. [124] U. Rothlisberger, P. Carloni, K. Doclo, M. Parrinello, A comparative study of galactose oxidase and active site analogs based on QM/MM Car-Parrinello simulations, J. Biol. Inorg. Chem. 5 (2000) 236–250. [125] M. Szaleniec, A. Dudzik, B. Kozik, T. Borowski, J. Heider, M. Witko, Mechanistic basis for the enantioselectivity of the anaerobic hydroxylation of alkylaromatic compounds by ethylbenzene dehydrogenase, J. Inorg. Biochem. 139 (2014) 9–20. [126] X. Mu, C. Zhang, D. Xu, QM/MM investigation of the catalytic mechanism of angiotensin-converting enzyme, J. Mol. Model. 22 (2016) 132. [127] W. Chotpatiwetchkul, N. Jongkon, S. Hannongbua, M.P. Gleeson, QM/MM investigation of the reaction rates of substrates of 2,3-dimethylmalate lyase:

[128]

[129]

[130]

[131]

[132]

[133]

[134] [135] [136] [137]

[138]

[139] [140] [141] [142]

[143]

[144]

[145]

a catabolic protein isolated from Aspergillus niger, J. Mol. Graph. Model. 68 (2016) 29–38. R. Lonsdale, J.N. Harvey, A.J. Mulholland, Effects of dispersion in density functional based quantum mechanical/molecular mechanical calculations on Cytochrome P450 catalyzed reactions, J. Chem. Theory Comput. 8 (2012) 4637–4645. J. Oláh, A.J. Mulholland, J.N. Harvey, Understanding the determinants of selectivity in drug metabolism through modeling of dextromethorphan oxidation by cytochrome P450, Proc. Natl. Acad. Sci. U.S.A. 108 (2011) 6050– 6055. J.B. Siegel, A. Zanghellini, H.M. Lovick, G. Kiss, A.R. Lambert, J.L. StClair, J.L. Gallaher, D. Hilvert, M.H. Gelb, B.L. Stoddard, K.N. Houk, F.E. Michael, D. Baker, Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction, Science 329 (2010) 309–313. S. Mazurek, T.R. Ward, M. Novicˇ, Counter propagation artificial neural networks modelling of an enantioselectivity of artificial metalloenzymes, Mol. Divers 11 (2007) 141–152. J.H. Hartman, S.D. Cothren, S.-H. Park, C.-H. Yun, J.A. Darsey, G.P. Miller, Predicting CYP2C19 catalytic parameters for enantioselective oxidations using artificial neural networks and a chirality code, Bioorg. Med. Chem. 21 (2013) 3749–3759. C. Andreini, G. Cavallaro, S. Lorenzini, A. Rosato, MetalPDB: a database of metal sites in biological macromolecular structures, Nucleic Acids Res. 41 (2013) D312–D319. D.E. Almonacid, P.C. Babbitt, Toward mechanistic classification of enzyme functions, Curr. Opin. Chem. Biol. 15 (2011) 435–442. http://www.ebi.ac.uk/thornton-srv/databases/Metal_MACiE/home.html (accessed 19.04.17). C. Andreini, I. Bertini, A bioinformatics view of zinc enzymes, J. Inorg. Biochem. 111 (2012) 150–156. G.L. Holliday, J.D. Fischer, J.B.O. Mitchell, J.M. Thornton, Characterizing the complexity of enzymes on the basis of their mechanisms and structures with a bio-computational analysis, FEBS J. 278 (2011) 3835–3845. G.L. Holliday, C. Andreini, J.D. Fischer, S.A. Rahman, D.E. Almonacid, S.T. Williams, W.R. Pearson, MACiE: exploring the diversity of biochemical reactions, Nucleic Acids Res. 41 (2012) D783–D789. A.W. Foster, D. Osman, N.J. Robinson, Metal preferences and metallation, J. Biol. Chem. 289 (2014) 28095–28103. http://www.rcsb.org/pdb/home/home.do (accessed 19.04.17). http://metalweb.cerm.unifi.it/ (accessed 19.04.17). A. Rosato, Y. Valasatava, C. Andreini, Minimal functional sites in metalloproteins and their usage in structural bioinformatics, Int. J. Mol. Sci. 17 (2016) 671–678. A. Ilari, L. Pescatori, R. Di Santo, A. Battistoni, S. Ammendola, M. Falconi, F. Berlutti, P. Valenti, E. Chiancone, Salmonella enterica serovar Typhimurium growth is inhibited by the concomitant binding of Zn(II) and a pyrrolylhydroxamate to ZnuA, the soluble component of the ZnuABC transporter, BBA – Gen. Subjects 2016 (1860) 534–541. A. Ilari, F. Alaleona, P. Petrarca, A. Battistoni, E. Chiancone, The X-ray structure of the zinc transporter ZnuA from salmonella enteric discloses a unique triad of zinc-coordinating histidines, J. Mol. Biol. 409 (2011) 630–641. R. Jesu Jaya Sudan, J. Lesitha Jeeva Kumari, C. Sudandiradoss, Ab Initio coordination chemistry for nickel chelation motifs, PLoS ONE 10 (2015) e0126787–e0126795.

Please cite this article in press as: K. Wieszczycka, K. Staszak, Artificial metalloenzymes as catalysts in non-natural compounds synthesis, Coord. Chem. Rev. (2017), http://dx.doi.org/10.1016/j.ccr.2017.06.012