Structure and function of glycoglycerolipids in plants and bacteria

Progress in Lipid Research Progress in Lipid Research 46 (2007) 225–243 www.elsevier.com/locate/plipres

Review

Structure and function of glycoglycerolipids in plants and bacteria Georg Ho¨lzl, Peter Do¨rmann

*

Max Planck Institute of Molecular Plant Physiology, Am Mu¨hlenberg 1, 14476 Potsdam-Golm, Germany Received 28 March 2007; received in revised form 9 May 2007; accepted 11 May 2007

Abstract Phosphoglycerolipids are abundant membrane constituents in prokaryotic and eukaryotic cells. However, glycoglycerolipids are the predominant lipids in chloroplasts of plants and eukaryotic algae and in cyanobacteria. Membrane composition in chloroplasts and cyanobacteria is highly conserved, with monogalactosyldiacylglycerol (MGD) and digalactosyldiacylglycerol (DGD) representing the most abundant lipids. The genes encoding enzymes of galactolipid biosynthesis have been isolated from Arabidopsis. Galactolipids are crucial for growth under normal and phosphate limiting conditions. Furthermore, they are indispensable for maximal efficiency of photosynthesis. A wide variety of glycoglycerolipids is found in different bacteria. These lipids contain glucose or galactose, in some cases also mannose or other sugars with different glycosidic linkages in their head group. Some bacterial species produce unusual glycoglycerolipids, such as glycophospholipids or glycoglycerolipids carrying sugar head groups esterified with acyl residues. A number of genes coding for bacterial glycoglycerolipid synthases have been cloned and the enzymes characterized. In contrast to the breadth of information available on their structural diversity, much less is known about functional aspects of bacterial glycoglycerolipids. In some bacteria, glycoglycerolipids are required for membrane bilayer stability, they serve as precursors for the formation of complex membrane components, or they are crucial to support anoxygenic photosynthesis or growth during phosphate deficiency. Ó 2007 Elsevier Ltd. All rights reserved.

Keywords: Galactolipid; Phospholipid; Photosynthesis; Anoxygenic; Chloroplast; Thylakoid; Phosphate

Abbreviations: CL, cardiolipin (diphosphatidylglycerol); DAG, diacylglycerol; DGD, digalactosyldiacylglycerol; DGDS, digalactosyldiacylglycerol synthase; Gal, galactosyl; GalD, galactosyldiacylglycerol; GGGT, galactolipid:galactolipid galactosyltransferase; Glc, glucosyl; GlcAD, glucuronosyldiacylglycerol; GlcD, glucosyldiacylglycerol; LHCII, light harvesting complex II; Man, mannosyl; ManD, mannosyldiacylglycerol; MGD, monogalactosyldiacylglycerol; MGDS, monogalactosyldiacylglycerol synthase; MGlcD, monoglucosyldiacylglycerol; MGlcDS, monoglucosyldiacylglycerol synthase; PSI or II, photosystem I or II; SQD, sulfoquinovosyldiacylglycerol; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; TAU, taurine amide of glucuronic acid; UDP-Gal, uridine diphospho-galactose; UDP-Glc, uridine diphospho-glucose. * Corresponding author. Tel.: +49 331 567 8259; fax: +49 331 567 8250. E-mail address: [email protected] (P. Do¨rmann). 0163-7827/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.plipres.2007.05.001

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Contents 1. 2.

3.

4. 5. 6.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Galactolipids in plants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Structure of galactolipids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Galactolipid biosynthesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Glycolipids in photosynthetic and non-photosynthetic bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Oxygenic photosynthetic bacteria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Anoxygenic photosynthetic bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Non-photosynthetic bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The role of galactolipids and other glycolipids in photosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The role of galactolipids and other glycolipids during phosphate deprivation . . . . . . . . . . . . . . . . . . . . . . . Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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1. Introduction Phospholipids and glycolipids represent the major building blocks for biological membranes. Based on the structure of the hydrophobic part, different classes of membrane lipids can be distinguished: glycerolipids, sphingolipids, and sterol lipids, with the glycerolipids constituting the most abundant group. In animals and yeast, as well as in extraplastidial membranes of plants, phosphoglycerolipids are the predominating lipid class. In contrast, chloroplasts are characterized by the occurrence of high proportions of galactolipids. MGD and DGD constitute about 50% and 30% of total lipids in thylakoids, respectively [1]. Further thylakoid lipids are the acidic sulfoglycolipid sulfoquinovosyldiacylglycerol (SQD) and phosphatidylglycerol (PG). Phosphatidylcholine (PC) is found in minor amounts in the outer chloroplast envelope. With the exception of PC which is absent from cyanobacteria, this chloroplast-specific lipid composition is more or less conserved in cyanobacteria. Synechocystis cells for example contain 59% MGD, 17% DGD, 16% SQD and 8% PG [2]. Furthermore, the anomeric head group configuration of cyanobacterial glycoglycerolipids is identical to that of the corresponding plant lipids. The conservation in glycerolipid composition and structure between cyanobacteria and chloroplasts can be explained according to the endosymbiont hypothesis. Following this hypothesis, a photosynthetically active ancestral, cyanobacterial cell was engulfed by a eukaryotic progenitor giving rise to the first plant cell. During this process, a number of physiological processes were transferred into the plant cell which can explain why chloroplasts of plants and today’s cyanobacteria share many common physiological aspects. Due to their high abundance, galactolipids play an important role in the establishment of membrane characteristics. For example, galactolipid content and composition affects the ratio of bilayer to non-bilayer forming lipids which is crucial for maintaining membrane stability and functional activity of membrane proteins [3]. Furthermore, the bilayer characteristics depend on the degree of desaturation and the chain length of the fatty acids (in this respect, plants and cyanobacteria show high variability). Glycolipids with only one sugar in the head group, such as MGD, exhibit non-bilayer forming properties (with the exception of the sulfolipid SQD). On the other hand, diglycosyldiacylglycerols such as DGD are always bilayer forming. These properties, however, do not explain the preference of plants and cyanobacteria for galactose over glucose in the lipid head group. The high abundance of galactolipids is restricted to organisms performing oxygenic photosynthesis suggesting that not only phylogenetic relations, but also functional aspects are the basis for their high abundance in the photosynthetic membrane. In addition, galactolipids were found to play a fundamental role under phosphate limiting conditions serving as surrogate for phospholipids. In contrast to the limited set of glycerolipids found in oxygenic photosynthetic organisms, the anoxygenic photosynthetic bacteria contain a large variety of phospho- and glycoglycerolipids in their membranes. Some species synthesize MGD or uncharacterized glycoglycerolipids, others are completely devoid of glycolipids. A

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Table 1 Distribution of glycoglycerolipids in plants and bacteria Organism

Major glycoglycerolipids

Plants and cyanobacteria

bGalD, aGal(1 ! 6)bGalD, SQD

Anoxygenic photosynthetic bacteria Chloroflexi (green non-sulfur bacteria) Chloroflexaceae Chlorobi (green sulfur bacteria) Chlorobiaceae Purple non-sulfur bacteria (Alphaproteobacteria) Rhodospirillales Blastochloris viridis (Rhizobiales) Rhodobacter sphaeroides (Rhodobacterales) Purple sulfur bacteria (Gammaproteobacteria) Chromatiaceae Firmicutes (Gram-positive bacteria) Bacillus, Staphylococcus Alicyclobacillus acidocaldarius Planococcus Lactobacillus casei, Streptococcus pneumoniae Streptococcus faecalis, Acholeplasma Actinobacteria (high G+C Gram-positive) Micrococcaceae, Microbacteriaceae, Nocardiopsaceae, Pseudonocardiaceae Propionibacterium Streptomycetes Bifidobacterium

Reference

bGalD, bGlc(1 ! 6)bGalD

[37,38]

Monogalactosyldiacylglycerol, oligoglycosyldiacylglycerols

[38,41]

SQD bGalD, bGal(1 ! 6)bGalD, aGlcAD SQD, aGlc(1 ! 4)bGalD

[46,47] [43] [48,49]

Mono- and diglycosyldiacylglycerol, SQD

[46,51].

bGlc(1 ! 6)bGlcD bGlc(1 ! 4)b-N-acylglucosaminyldiacylglycerol SQD aGal(1 ! 2)aGlcD aGlcD, aGlc(1 ! 2)aGlcD

[53] [60] [61] [52,62] [63–65,67]

Different acyl derivatives of aMan(1 ! 3)aMan-glycerol or aGlc(1 ! 3)aMan-glycerol aGlc(1 ! 3)aGlc-acyl-alkyl-glycerol aGlcAD, aGlc(1 ! 4)aGlcAD bGalD, bGal(1 ! 2)bGalD, bGal(1 ! 2)bGal(1 ! 2)bGalD

[76–79,83–87] [88] [90] [94–96]

Deinococcus-Thermus Deinococcus radiodurans

aGlcD

[73,74]

Thermotogae Thermotaga maritima

aGlc(1 ! 4)aGlcD

[75]

aGlcD, aGlcAD, aGlc(1 ! 4)aGlcAD, SQD, TAU

[100,102–108]

aGlc(1 ! 3)aManD SQD

[109,110] [112]

aGalD, aGlcD

[114–116,119,120]

Alphaproteobacteria Cauliform bacteria and relatives Brevundimonas, Hyphomonas, Maricaulis, Woodsholea, Caulobacter Rhizobiales Rhizobium Sinorhizobium Spirochaetes Treponema, Spirochaeta, Serpula, Borrelia

The taxonomy for the different bacterial groups is based on information available at the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov).

number of studies suggest that glycoglycerolipids play a specific role in anoxygenic photosynthesis. Galactolipids with a head group structure related to plant and cyanobacterial MGD and DGD are absent from nonphotosynthetic bacteria, with few exceptions for MGD. In general, bacterial glycoglycerolipids mostly contain one or two sugars or sugar derivatives bound to diacylglycerol. The head group diversity of these glycoglycerolipids is further determined by the variety of different glycosidic linkages. The sugars occur in a- or b-anomeric configuration and are bound in (1 ! 2), (1 ! 3), (1 ! 4) or (1 ! 6) linkage. Besides, some bacterial species contain glycolipids with more than two sugars. However, in contrast to the high diversity of sugars in the head group, the composition of the hydrophobic lipid part in most non-photosynthetic bacteria is rather simple with a preponderance of saturated or monounsaturated fatty acids. A compilation of the main glycolipids and their occurrence in different organisms, and a collection of the most relevant glycolipid head group

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Fig. 1. Structural diversity of glycoglycerolipid head groups. (a) Structures of the most common sugars present in glycoglycerolipids. (b) The major head group structures found in bacterial and plant glycoglycerolipids. D or DAG, diacylglycerol; Gal, galactosyl; Glc, glucosyl; GlcA, glucuronosyl; Man, mannosyl; SQD, sulfoquinovosyldiacylglycerol. The sugars are depicted as black, white or grey hexagons.

structures are shown in Table 1 and Fig. 1. Related information on the structure and distribution of lipids in different organisms can be retrieved from a number of databases via the world-wide web (www.lipidat.chemistry.ohio-state.edu; http://lipidbank.jp; www.lipidmaps.org; www.cyberlipid.org). Furthermore, ether-linked glycoglycerolipids are abundant in different species of Archaea. However, these complex glycolipids will not be

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part of this review. Similar to higher plants and cyanobacteria, some species of anoxygenic or non-photosynthetic bacteria are capable of replacing their phospholipids with glycolipids under phosphate deficient conditions. The occurrence of a large variety of bacterial glycoglycerolipids suggests that these lipids do not just serve as building blocks for biological membranes, but that they are crucial for different physiological functions in the cell. 2. Galactolipids in plants 2.1. Structure of galactolipids The galactolipids MGD and DGD are found in all organisms performing oxygenic photosynthesis. In plants, their occurrence is in general restricted to the plastids, where they are the predominating lipid class. The galactose residue in MGD is bound to the sn-3 position of the glycerol backbone in b-anomeric linkage (bGalD). The head group of DGD is characterized by a terminal a-galactose moiety (1 ! 6) linked to the inner b-galactose residue (aGal(1 ! 6)bGalD). Some plants (e.g. Adzuki bean) contain an additional DGD form with the two galactose residues in b-anomeric configuration (bGal(1 ! 6)bGalD) and oligogalactolipids with three or more galactose residues in different anomeric configurations (see review [4]). These unusual galactolipids are synthesized only under certain growth conditions or in specific tissues. In contrast to the conserved head group structures of MGD and DGD, the fatty acids of galactolipids exhibit a high variability in chain lengths, degree of unsaturation and distribution to the sn-1 and sn-2 position of the glycerol backbone. 2.2. Galactolipid biosynthesis The two plant galactolipids MGD and DGD are synthesized in the envelope membranes of plastids [5–8]. Their precursors, however, only in part originate from the plastid. Furthermore, the newly formed galactolipids are redistributed to the thylakoid membranes, and under certain growth conditions, DGD is exported to extraplastidial membranes. Galactolipid biosynthesis thus requires a coordinated transport of lipids within the plastids and between different organelles. For the synthesis of the different molecular species of galactolipids, plants harbor a set of galactolipid synthases (galactosyltransferases) which differ in their specificity and localization. The initial step of galactolipid synthesis is catalyzed by the MGD synthase (MGDS) which transfers a galactosyl residue from uridine diphospho-galactose (UDP-Gal) onto the sn-3 position of diacylglycerol (DAG). The galactosylation reaction follows an inverting mechanism accompanied with the change of the anomeric sugar configuration from a in UDP-Gal to b in MGD. Glycosyltransferases from a number of organisms have been organized into different families based on sequence similarities [9]. Accordingly, plant MGDSs belong to the family 28 (GT28) of the CAZy database of glycosyltransferases. The first MGDS was isolated from cucumber seedlings [10]. The MGDS sequence is similar to that of MurG from Bacillus subtilis and Escherichia coli indicating a common evolutionary origin [10]. Further sequence similarities exist with bacterial lipid glycosyltransferases from Staphylococcus aureus and Bacillus subtilis [11,12]. These bacterial glycosyltransferases, however, are specific for uridine diphospho-glucose (UDP-Glc) and characterized by a processive reaction mechanism, i.e. in contrast to plant MGDS, these enzymes transfer more than one sugar residue onto DAG leading to the production of oligoglycolipids. The sequential glycosylation of DAG and glycolipids by one enzyme resulting in the production of oligoglycolipids was designated ‘‘processive’’ activity. Furthermore, the GT28 family contains the first representative of a bacterial MGDS, recently cloned from Chloroflexus aurantiacus [13]. Two types of MGDSs (types A and B) can be distinguished based on sequence similarity. MGD1 of Arabidopsis (type A) which is highly expressed in all developmental stages and in green tissues [5] synthesizes the largest proportion of MGD in the chloroplast [14]. Expression of type B enzymes (MGD2 and MGD3) depends on the developmental stage and is restricted to specific plant organs. Type B galactolipid synthase expression is only found in the tips of leaves and in non-photosynthetic tissues where transcripts of MGD2 were localized to inflorescences and those of MGD3 to roots. Apart from that, the two type B enzymes are expressed in germinating pollen and in pollen tubes where they contribute to the synthesis of extraplastidial galactolipids required for membrane proliferation in growing pollen tubes. With the

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exception of pea MGDS activity which was detected in the outer and inner plastid envelopes [15,16] all type A MGDSs were localized to the inner envelope [5,10]. On the other hand, type B enzymes are associated with the outer envelope. First insight into the mechanism of in vivo DGD biosynthesis was obtained by the characterization of an Arabidopsis mutant (dgd1) reduced in DGD content [17]. Based on the availability of the dgd1 mutant, the corresponding gene (DGD1) which encodes an enzyme responsible for the major cellular DGD synthase (DGDS) activity was isolated [18]. The dgd1 plant still contains residual DGDS activity which was attributed to a second DGDS gene in the Arabidopsis genome (DGD2) [8]. The two DGDSs are UDP-Gal dependent galactosyltransferases employing MGD as substrate. DGD synthesis follows a retaining mechanism, i.e. the a-anomeric configuration of galactose in UDP-Gal is preserved in DGD. According to Coutinho and Henrissat [9] both DGDSs are classified as a-glycosyltransferases in the family GT4. DGDS enzymes from Arabidopsis contain N-terminal extensions of different lengths that are required for their targeting to the outer envelope of plastids. Inactivation of the two genes in the dgd1 dgd2 double mutant resulted in the complete loss of DGD, demonstrating that DGD1 and DGD2 are sufficient to provide in vivo DGD synthesis activity in Arabidopsis. Previous studies on DGD synthesis led to the identification of a further activity, i.e. the galactolipiddependent, processive galactolipid:galactolipid galactosyltransferase (GGGT). This enzyme transfers one galactose moiety from MGD to a second molecule of MGD, thereby producing DGD, and after further galactosylation, oligogalactolipids with three or more galactose residues [19–22]. The gene encoding GGGT has not been isolated so far, but it is clear that this activity is independent from the known DGDS enzymes DGD1 and DGD2. Oligogalactolipids were detected in leaves of plants and in cyanobacteria, although only in minor amounts [23,24]. In contrast to DGD with aGalbGal structure produced by DGD1 or DGD2, oligogalactolipids are characterized by b(1 ! 6) linkages. Accumulation of oligogalactolipids was observed in vivo in the Arabidopsis tgd1 mutant carrying a defect in a lipid transport protein complex [21]. However, the role of the processive GGGT activity in galactolipid biosynthesis is not clear. 3. Glycolipids in photosynthetic and non-photosynthetic bacteria 3.1. Oxygenic photosynthetic bacteria The group of oxygenic photosynthetic bacteria encompasses the large but monophyletic, uniform class of Gram-negative cyanobacteria. Like plants and eukaryotic algae, these bacteria perform oxygenic photosynthesis employing H2O as electron donor accompanied with the release of oxygen (O2). Cyanobacteria contain two photosystems (PSI, PSII), which are structurally very similar to the plant photosystems. Furthermore, cyanobacterial cells are surrounded by two envelopes designated cytoplasmatic and outer membrane, and contain thylakoid membranes resembling those of chloroplasts. The unique lipid composition with high proportions of glycoglycerolipids (DGD, MGD, and SQD) and PG sets cyanobacteria apart from most other bacteria which contain phospholipids as their main membrane constituents. The genes for SQD and PG synthesis have been isolated from plants and cyanobacteria [25–28]. Although the lipid composition of cyanobacteria and chloroplasts is highly conserved, the pathways for galactolipid synthesis are distinct. Feige et al. [29] showed that monoglucosyldiacylglycerol (MGlcD), but not MGD, is the first glycolipid synthesized in radiolabeling experiments. Only in a second epimerization step, MGlcD is converted into MGD. MGlcD accounts for less than 1% of membrane lipids [29,30], but it can accumulate to up to 12% in Synechocystis cells growing in medium supplied with glucose [31]. Recently, the gene for MGlcD synthesis was identified in Anabaena and Synechocystis by comparative genomic analysis [32]. MGlcD synthase (MGlcDS) transfers glucose from UDP-Glc onto the sn-3 position of DAG following an inverting reaction mechanism, leading to the formation of MGlcD with b-anomeric head group (bGlcD). The cyanobacterial MGlcDS belongs to the family GT2 [9] which encompasses processive and non-processive b-glycosyltransferases including enzymes not involved in lipid synthesis such as cellulose synthases (EC 2.4.1.12). MGlcDS protein sequences are conserved in cyanobacteria but show no similarity to any plant glycoglycerolipid synthases. The enzyme prefers DAG with C18 acyl groups at sn-1 and C16 at sn-2 over DAG with C16 at both sn-positions. Therefore, the prevalent fraction of glycolipids produced in cyanobacteria shows a C18/C16 fatty acid distribution [24,32,33]. The enzyme

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activity is located to the cytoplasmatic membrane and to the thylakoids [34,35]. The gene coding for the cyanobacterial epimerase which catalyzes the conversion of MGlcD (bGlcD) to MGD (bGalD) has not yet been identified. This enzyme is characterized by low substrate selectivity regarding the anomeric sugar configuration because the corresponding a-anomer, aGlcD is also converted into aGalD [13]. DGD is formed by transfer of galactose onto MGD [30]. The gene encoding DGDS still awaits its identification. In contrast to most bacteria which synthesize lipids with saturated or monounsaturated fatty acids, cyanobacteria are characterized by a high degree of lipid unsaturation. It has been shown that the number of double bonds in the acyl chains is affected by different stress conditions (e.g., heat, cold) [36]. 3.2. Anoxygenic photosynthetic bacteria Anoxygenic photosynthetic bacteria constitute a heterogeneous collection of species belonging to different branches of the bacterial kingdom. Based on physiological characteristics, four main groups can be distinguished, i.e. the purple sulfur, the purple non-sulfur, the green sulfur and the green non-sulfur bacteria. The representatives of the purple sulfur bacteria belong to the order Chromatiales in the Gammaproteobacteria cluster. The purple non-sulfur bacteria comprise different genera of the Alphaproteobacteria in the orders Rhodobacterales, Rhodospirillales and Rhizobiales. Members of the Chlorobi group are designated as green sulfur bacteria, and the Chloroflexi group represents the green non-sulfur bacteria. Photosynthetic species are also found among the Gram-positive bacteria in the order Chlostridiales, such as Heliobacterium. All genera have in common that they do not use H2O as electron donor for photosynthesis and thus do not produce free oxygen. Instead, they employ sulfur compounds, H2, or organic molecules as electron donor, and they release the corresponding oxidized molecules. Another important characteristic of anoxygenic photosynthetic bacteria is the presence of only one photosystem related to PSI or PSII of plants and cyanobacteria. In many earlier studies, lipids were only characterized by co-migration with standards and the head group was analyzed by specific staining after thin-layer chromatography. Thus, the lipids of many anoxygenic photosynthetic bacteria still await their structural elucidation. Like plants and cyanobacteria, members of the green non-sulfur bacteria contain high amounts of the galactolipid MGD [37,38]. Recently, the gene coding for MGDS was isolated from Chloroflexus aurantiacus and the enzyme activity characterized [13]. Similar to plant MGDS, this bacterial galactosyltransferase is specific for b-glycosidic bonds and is a member of the GT28 family [9]. A diglycosyldiacylglycerol lipid containing glucose and galactose in equal amounts in its head group represents an additional abundant membrane component in Chloroflexus [38]. After isolation of the corresponding gene from C. aurantiacus and heterologous expression in cyanobacteria and plants, it became clear that this glycosyltransferase forms bGlc(1 ! 6)bGalD using MGD and UDP-Glc as substrates [13]. The enzyme is specific for b-glycosidic linkages and belongs to the family GT28, but it shows no processivity in contrast to the glucosyltransferase from Staphylococcus aureus [11] which belongs to the same family [9]. Reports on the occurrence of SQD in Chloroflexus could not be confirmed [39]. Chloroflexus contains two phospholipids, PG and PI. The occurrence of PI is very unusual for phototrophic bacteria [37]. The Chlorobiaceae, representatives of the green sulfur bacteria, were newly classified based on phylogenetic relationships of 16S rRNA and on other genetic characteristics [40]. Some species have been transferred to different genera, such as Chlorobium tepidum which has been renamed Chlorobaculum tepidum. MGD was identified as an important glycolipid in some green sulfur bacteria. Additional glycolipids were detected which were not characterized in more detail. One of these glycolipids contains rhamnose, glucose, galactose and an unidentified sugar in its head group [38,41]. Furthermore, green sulfur bacteria contain cardiolipin (CL), phosphatidylethanolamine (PE) and PG, whereas SQD is absent [39]. The genes and enzymes for glycolipid biosynthesis have not been identified. Lipid composition in different species of purple non-sulfur bacteria varies considerably. While many species of this bacterial group are devoid of glycoglycerolipids, some produce glycoglycerolipids under specific growth conditions. These bacterial species which include many non-photosynthetic bacteria belong to different families. Blastochloris viridis (former designation: Rhodopseudomonas viridis) belongs to the Hyphomicrobiaceae in the order Rhizobiales [42]. This organism contains minor amounts of MGD with identical head group structure (bGalD) as found in plants and cyanobacteria. The digalactosyldiacylglycerol of Blastochloris, however,

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is structurally different from plant DGD because the terminal galactose has b-anomeric configuration (bGalbGalD) [43]. This bacterial lipid has the same structure as the unusual plant galactolipid bGal(1 ! 6)b GalD isolated from Adzuki bean [44,45]. The genes and enzymes for MGD and bGal(1 ! 6)bGalD synthesis have not yet been identified. Presumably, MGD is formed by direct galactosylation of DAG, in contrast to cyanobacteria where first MGlcD is formed which is converted to MGD via epimerization (see above). An additional, acidic glycolipid found in appreciable amounts in Blastochloris is a-glucuronosyldiacylglycerol (aGlcAD). PC and ornithine lipid are the major lipids, while PE, PG and CL are found in lower amounts, and SQD is totally absent [43]. Blastochloris shows a remarkably wide fatty acid diversity in its glycerolipids. The fatty acid composition differs from cyanobacteria and chloroplast-derived lipids of plants by the occurrence of C18 fatty acids at the sn-2 position of glycerol [43]. In other phototrophic representatives, such as Rhodopseudomonas palustris (Bradyrhizobiaceae) which belongs in the same order, no glycoglycerolipids were detected [41]. Furthermore, some members of the order Rhodospirillales were shown to contain SQD, but MGD or other glycolipids were not detected [46,47]. Rhodobacter sphaeroides (a representative of the Rhodobacterales) contains phospholipids, ornithine lipid and SQD under normal growth conditions [48]. Two glycoglycerolipids accumulate under phosphate starvation [49,50]. One of them was identified as glucosylgalactosyldiacylglycerol (aGlc(1 ! 4)bGalD), but it differs in linkage and anomeric configuration from the corresponding Chloroflexus lipid [13]. The sugar structure of the second Rhodobacter glycoglycerolipid (a monoglycosyldiacylglycerol) was not resolved. Two groups of bacteria belong to the purple sulfur bacteria, Chromatiaceae and Ectothiorhodospiraceae. While species of Chromatiaceae are characterized by the presence of glycolipids, Ectothiorhodospiraceae are devoid of glycolipids [46,51]. All genera of Chromatiaceae analyzed to date accumulate mono- and diglycosyldiacylglycerol, additional unidentified glycoglycerolipids, and SQD. The monoglycosyldiacylglycerol was suggested to contain mostly glucose; the oligoglycerolipids presumably contain one molecule of glucose and one or two mannose residues. The phospholipids present in the two families comprise PG, CL, PE, lyso-PE, and in Ectothiorhodospiraceae, PC. 3.3. Non-photosynthetic bacteria The degree of structural variability of glycoglycerolipids found in non-photosynthetic bacteria surpasses that in photosynthetic bacteria. Glycoglycerolipids occur in many species of Firmicutes (Gram-positive bacteria), but they are also found in representatives of the Phyla Spirochaetes, Actinobacteria, Proteobacteria, Deinococcus-Thermus and Thermotogae. The Firmicutes comprise the three classes Bacilli, Clostridia and Mollicutes. Bacillus subtilis and different Staphylococcus strains, all belonging to the order of Bacillales, contain bGlc(1 ! 6)bGlcD as the major glycoglycerolipid [52–57]. However, the proportion of this lipid still accounts for less than 10% of total lipids. Corresponding mono- and triglucosylated diacylglycerols can also be detected, but in very low amounts. By homology searches in genomic databases employing the cucumber MGDS sequence [10], one glucolipid synthase genes each was identified in Staphylococcus and Bacillus. The corresponding enzymes belong to the family GT28, along with plant MGDSs [9]. The characterization of the glucosyltransferases showed that they are responsible for the synthesis of mono-, di- and oligoglucolipids with DAG as primary acceptor, and with identical head group configuration as found in the native bacterial glycolipids [11,12,58]. A major function of bacterial diglucosyldiacylglycerol is to serve as membrane anchor for lipoteichoic acids [58]. The lipid composition of the extremely thermophilic species Alicyclobacillus acidocaldarius (the former Bacillus acidocaldarius) [59] differs considerably from that of the other members of Bacillales. Alicyclobacillus is characterized by a high proportion of glycolipids (64% of total lipids) with very unusual compositions of the head group and of the lipophilic part [60]. Different derivatives of the following two basic structures occur which are bGlc(1 ! 4)b-N-acylglucosaminyldiacylglycerol, and b-N-acylglucosamine bound to a pentacyclic tetrol. Additionally, this organism produces SQD (close to 10% of total lipids), a glycolipid which is rather unusual for bacteria. In Planococcus [61], a member of the same order, SQD is even more abundant (51% of polar lipids) than the proportion of phospholipids. Representatives of Lactobacillales synthesize glycoglycerolipids with a-anomeric configuration. In Streptococcus pneumoniae and Lactobacillus casei, aGal(1 ! 2)aGlcD was identified as the main glycolipid [54,62].

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L. casei additionally synthesizes aGlc(1 ! 6)aGal(1 ! 2)aGlcD. Streptococcus faecalis contains aGlcD, aGlc(1 ! 2)aGlcD and a diglucosyldiacylglycerol lipid with unknown structure [63]. The two lipids, aGlcD and aGlc(1 ! 2)aGlcD, are also found in representatives of the Mollicutes in the genus Acholeplasma [64,65]. The cell wall-less bacterium Acholeplasma laidlawii contains almost 50% of glycolipids, and is one of the best investigated non-photosynthetic bacteria with regard to the regulation of glycolipid synthesis and the function of glycolipids in biological membranes [66–69]. In contrast to the processive glycosyltransferase activities in S. aureus and B. subtilis, the synthesis of mono- and diglycosyldiacylglycerols in A. laidlawii and in S. pneumoniae, and probably also in other species of Mollicutes and Lactobacillales, is based on the presence of two enzymes [66,67,70]. In the first glycosylation step, MGlcDS transfers one glucose residue from UDP-Glc onto DAG to produce aGlcD which serves as substrate for the second glycosylation step catalyzed by a UDP-Gal or UDP-Glc specific glycosyltransferase. The isolation of MGlcDS from A. laidlawii facilitated the identification of orthologous genes from several Gram-positive and thermophilic bacteria [66,67]. The mono- and diglycosyldiacylglycerol synthases from A. laidlawii and S. pneumoniae were shown to be responsible for the formation of aGlcD, aGlc(1 ! 2)aGlcD and aGal(1 ! 2)aGlcD. The presence of aGlcD and diglucosyldiacylglycerol in Acholeplasma is crucial for the adjustment of the bilayer-to-non-bilayer forming lipid ratio in the membranes. In line with this hypothesis, the introduction of MGlcDS from Acholeplasma into a PE-deficient E. coli mutant resulted in the accumulation of aGlcD and in complementation of the growth deficiency of the E. coli mutant. The functional replacement of PE with aGlcD can be explained by the fact that these two lipids share non-bilayer forming characteristics [71,72]. Furthermore, although not related with the Firmicutes, MGlcDS genes were isolated from the radioresistant bacterium Deinococcus radiodurans and from Thermotoga maritima [13]. D. radiodurans shows a complex lipid composition of glycophospho- and glycoglycerolipids, with aGlcD as the simplest representative; diglucosyldiacylglycerol was not detected [73,74]. The extremely thermophilic bacterium T. maritima belongs to a phylum which represents one of the earliest branches of the bacterial kingdom. This organism contains a diglucosyldiacylglycerol lipid (aGlc(1 ! 4)aGlcD) with a structure rarely found in bacteria. aGlc(1 ! 4)aGlcD, together with its acylated derivative (acyl group on C6 of the terminal glucose), comprises about 50% of total lipids [75]. aGlcD is synthesized in Thermotoga by an MGlcDS activity. However, the fact that aGlcD does not accumulate in Thermotoga suggests that it only serves as a precursor for diglucosyldiacylglycerol formation. The a-glycosyltransferases involved in aGlcD formation belong to the family GT4 of retaining glycosyltransferases [9], as already described for the plant DGDS. The class of Actinobacteria comprises the G+C rich Gram-positive bacteria. The largest order Actinobacteriales which can be divided into many suborders and families contains bacterial species with relevance to human health. Among these, highly pathogenic representatives are found such as Mycobacterium tuberculosis. In addition, many species, particularly within the genus Streptomyces, provide a diverse source for the isolation of antibiotics. The small order Bifidobacteriales contains organisms which are part of the intestinal flora and therefore are also important for human health. Apart from the glycolipids discussed here, the Actinobacteria contain highly complex glycolipids which are not part of this review. Glycoglycerolipids and glycoglycerolipids with acylated sugar derivatives are relatively common. The most frequent head group structure consists of two sugars with a-mannose prevailing. Glucose or galactose are found to lesser extents. The predominant linkage between the two sugar residues is (1 ! 3). Members of Micrococcaceae, such as Micrococcus luteus (formerly Micrococcus lysodeikticus), synthesize aMan(1 ! 3)aManD as the main glycoglycerolipid [76–78]. The synthesis occurs in a non-processive manner by two enzymes transferring mannose in a guanine diphospho-mannose dependent reaction onto DAG and aManD, respectively. aManD is of low abundance and thus supposedly only represents an intermediate of glycolipid synthesis. Dimannosyldiacylglycerol is highly important as lipid anchor during lipomannan formation [79]. Arthrobacter (Micrococcaceae) also synthesizes dimannosyldiacylglycerol, and in addition produces mono- and digalactosyldiacylglycerol. However, the head group structures of these latter lipids have not been fully resolved [80,81]. Dimannosyldiacylglycerol is also found in Leifsonia aquatica, the former Corynebacterium aquaticum (Microbacteriaceae) [82], and in Nocardiopsis dassonvillei (Nocardiopsaceae) [83,84]. An additional strain of Nocardiopsis has been described that does not contain dimannosyldiacylglycerol, but a very unusual glycerol-free glycolipid with two fatty acids directly esterified to the two C6 positions of the aGlc(1 ! 1)aGlc unit. Several acyl derivatives of a aMan(1 ! 3)aMan-glycerol structure are known from different bacterial families. In some species of Rothia

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(Micrococcaceae) or Saccharopolyspora (Pseudonocardiaceae), one fatty acid is esterified to the C6 position of the internal mannose and another one is bound to the sn-1 or sn-2 position of glycerol (aMan (1 ! 3)(acyl)aMan-monoacylglycerol) [84–86]. A similar derivative containing glucose as the terminal sugar (aGlc(1 ! 3)(acyl)aMan-monoacylglycerol), was isolated from Microbacterium (Microbacteriaceae) [87]. In addition, this organism contains three less abundant glycolipids which were identified as C6-acetylated derivatives of the diglycosylglycolipid, as bGlc(1 ! 6)bGlcD, and as b-galactofuranosyldiacylglycerol. Very unusual glycolipids are also found in Propionibacterium propionicum (Propionibacteriaceae) where the sn-3 position of the glycerol is substituted by an alkyl ether chain, and the sn-2 position is acylated with a fatty acid [88]. The main components comprise the diglucosylglycerolipid aGlc(1 ! 3)aGlc-acyl-alkyl-glycerol, a derivative of this glycolipid carrying an acyl group at the C6 of the terminal glucose, and aGlc-acyl-alkyl-glycerol. The acyl-free compound aGlc(1 ! 3)aGlc-alkyl-glycerol occurs in minor amounts. A simple monogalactosyldiacylglycerol lipid with unknown anomeric structure was isolated from Actinomyces viscosus (Actinomycetaceae) in amounts of 5–10% of total lipids [89]. Streptomycetes show general differences in their glycolipid composition as compared to other members of Actinomycetes discussed above. They synthesize acidic glycolipids with (1 ! 4) glycosidic linkages, including aGlcAD, aGlc(1 ! 4)aGlcAD and a derivative of aGlc(1 ! 4)aGlcAD carrying a fatty acid bound to the C2 of glucuronic acid. Lipids of Streptomycetes were reviewed by Batrakov and Bergelson [90]. Glycolipids with very complex structures are synthesized in Mycobacteria and were reviewed by Lederer [91]. In vitro enzyme assays with extracts from Mycobacterium smegmatis revealed that this bacterium is capable of producing monoglycosyldiacylglycerol containing glucose as the major sugar, and galactose or mannose as minor components. Similarly, diglycosyldiacylglycerols produced in vitro mostly contained glucose [92]. The structure of diglucosyldiacylglycerol from M. smegmatis was established as bGlc(1 ! 6)bGlcD [93]. The lipid composition of Bifidobacterium of the order Bifidobacteriales is distinct from that of Actinobacteriales by a high content of galactolipids (45–60% of total lipids). The major glycolipids in Bifidobacterium are bGalD, bGal(1 ! 2)bGalD and bGal(1 ! 2)bGal(1 ! 2)bGalD. The occurrence of bGalD with an identical head group configuration as in plant MGD is rather unusual for non-photosynthetic bacteria. Further lipids found in Bifidobacterium are derivatives of mono- and digalactosyldiacylglycerol that carry one or two acyl chains esterified to the sugar head group [94–96]. These acyl derivatives of Bifidobacterium also exist in the form of galactofuranosides. Presumably, galactofuranosidecontaining glycolipids are produced from diacylglycerol and UDP-Gal where the galactose residue is in the furanose form. The gene encoding a mutase converting the pyranose form of UDP-Gal into the furanose form was recently isolated from Klebsiella pneumoniae [97]. Glycolipids are found in high amounts in the cauliform bacteria, also termed ‘‘stalked bacteria’’. Because of their characteristic prosthecate, different bacteria from various habitats were assigned to the genus Caulobacter. After analysis of 16S rRNA sequences, it became clear that the different strains are genotypically diverse. Therefore, many species were re-classified and renamed and new genera were proposed [98–101]. The different genera are organized in several families in the orders Caulobacterales and Rhodobacterales of the Alphaproteobacteria. In general, all species investigated so far contain aGlcD and different acidic glycoglycerolipids. The acidic glycoglycerolipids comprise aGlcAD, aGlc(1 ! 4)aGlcAD, two sulfoglycolipids (SQD and the taurine amide of aGlcAD, TAU), and glycophospholipids. PG is the only phospholipid detected in some species. All of these lipids with the exception of the sulfolipids can be found in Brevundimonas vesicularis and Brevundimonas diminuta, formerly known as Pseudomonas vesicularis and Pseudomonas diminuta, respectively [98,102,103]. Brevundimonas bacteroides, the former Caulobacter bacteroides [99], in addition synthesizes SQD [104]. In this organism, aGlcD and aGlc(1 ! 4)aGlcAD account for more than 50%, and the sum of all glycolipids can reach up to 95% of total lipids. A similarly high glycolipid content with up to 99% is found in some marine species like Maricaulis maris [105], the former Caulobacter halobacteroides [99]. Phospholipids are completely absent from Hyphomonas jannaschiana. This species synthesizes aGlcD, aGlcAD and TAU [106,107]. The marine bacterium Woodsholea maritima is characterized by a limited diversity of polar lipids. It contains aGlcD, TAU and SQD, the latter being the major lipid [100]. In Caulobacter crescentus, glycolipids constitute about 50% of total lipids and thus are about equally abundant as phospholipids. This bacterium synthesizes mainly aGlcD and PG, including the acylated derivatives of PG and aGlcAD [108]. The high abundance of glycolipids in some of these species implies that essential biological membraneassociated processes can be maintained in an environment almost devoid of phospholipids.

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Apart from some photosynthetic bacteria discussed above, there are few reports on the presence of glycolipids in non-photosynthetic representatives of Rhizobiales (Alphaproteobacteria). Rhizobiales are of ecological and agricultural importance because some members are capable of fixing nitrogen in symbiosis with legumes. First evidence for the occurrence of glycoglycerolipids in the family Rhizobiaceae was obtained with the identification of aGlc(1 ! 3)aManD in Rhizobium leguminosarum [109]. This lipid occurs only in subnanomolar concentrations, but it is important for the initiation of morphological responses in the host plant relevant to symbiosis [110]. Further members of this order include the plant pathogenic bacterium Agrobacterium tumefaciens and the symbiotic bacterium Mesorhizobium loti. These two species do not synthesize glycolipids in detectable amounts, but they each contain a genomic glycosyltransferase-like locus [111]. The sequences of these glycosyltransferases show similarity to glucosylceramide synthases of the family GT21 [9], but differ in their enzyme characteristics. Over-expression in Agrobacterium and E. coli led to the accumulation of oligoglycolipids with bGal(1 ! 6)bGalD and bGal(1 ! 6)bGal(1 ! 6)bGalD as main components. In addition to UDP-Gal, the two enzymes also accept UDP-Glc as sugar donor, thus glucose-containing lipids are formed as well. The in vivo roles of these glycolipid synthases are not known. Other Rhizobiales such as Sinorhizobium meliloti (former Rhizobium meliloti) contain low amounts of SQD [112]. Targeted disruption of one of the SQD biosynthetic genes did not reveal any specific function of SQD in nodule-associated and in free-living Sinorhizobium cells, and there was no detectable effect on root nodule symbiosis [113]. The Spirochaetes consisting of only a single order (Spirochaetales) represent another class of glycolipidcontaining bacteria. This order includes many pathogenic species, such as the members of the genera Borrelia, Leptospira and Treponema. The glycolipids show a very simple head group structure. Organisms of the order Spirochaetales synthesize monoglycosyldiacylglycerols containing mostly galactose and minor amounts of glucose, presumably bound in a-anomeric configuration. Glycolipids amount to ca. 50% of polar lipids, the remainder being phospholipids [114]. Members of the genus Treponema typically contain aGalD, or a mixture of aGalD and aGlcD [114,115]. aGlcD is often the only glycolipid found in several species of the genera Spirochaeta and in Serpula innocens, the former Treponema innocens [114,116,117]. Derivatives of aGalD acylated with short chain acyl residues of two, three or four C atoms occur in Serpula hyodysenteriae [116]. The absence of aGalD or of other glycolipids from a subspecies strain of Treponema pallidum is very unusual in view of the ubiquitous glycolipid distribution across different Treponema species [118]. Moreover, Treponema lipids contain considerable amounts of di- and triunsaturated C18 fatty acids [114] which are characteristic for cyanobacterial and plant lipids and normally absent from bacteria. Borrelia, another Spirochaete strain, contains aGalD as found in Treponema [119,120]. However, Borrelia shows a markedly different lipid composition, because this organism synthesizes sterol glucoside and an acylated sterol glucoside. These sterol lipids are in general absent from bacteria, but widely distributed in eukaryotes. Leptospira represents the only genus where no glycolipids were detected so far [114]. 4. The role of galactolipids and other glycolipids in photosynthesis The conversion of light into chemical energy during photosynthesis is associated with protein–pigment complexes which are embedded into an intricate membrane system, the thylakoids of chloroplasts and cyanobacteria, or into the membranous structures of anoxygenic photosynthetic bacteria. Thylakoid membranes are characterized by their conserved lipid composition (see above) with MGD and DGD as major constituents [121]. Research on the structure and function of photosynthetic protein–pigment complexes and on the mechanism of electron transport has seen major progress in recent years. However, much less is known about the function of membrane lipids. One of the primary functions of lipids is the establishment of the thylakoid membrane bilayer. The biophysical characteristics of membranes in part depend on the ratio of non-bilayer and bilayer forming lipids and on the protein content and composition. In thylakoids, MGD is the only nonbilayer forming lipid, analogous to the non-bilayer-forming lipids PE and CL in bacterial and extraplastidial plant membranes. A number of studies revealed that membrane lipids specifically interact with protein complexes of photosynthesis, as reviewed in [122–124]. In the crystal structure of cyanobacterial PSI, three molecules of PG and one MGD molecule were identified. The close proximity of PG and MGD to the PsbA or PsbB subunits in the reaction center, respectively, infers that the two electron transfer branches in the PSI complex are energetically

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distinct [125]. Several lipids with asymmetric distribution are present in the periphery of the bacterial photosynthetic reaction center of R. sphaeroides [126]. Glucosylgalactosyldiacylglycerol is tightly bound to the reaction center close to the bacteriochlorophyll of the active electron transfer branch. It is assumed that lipidcofactor interactions contribute to differences in electron flow through the two cofactor branches in Rhodobacter. A mutation in the CL binding site of the Rhodobacter reaction center polypeptide led to the loss of CL in the crystallized protein and affected the thermal stability of the complex [127]. Crystallized light harvesting ˚ , respectively, differ by their arrangement complexes II (LHCII) of spinach or pea resolved at 2.72 or 2.5 A of bound DGD lipids [128,129]. In spinach LHCII, two molecules of DGD localize to the contact sites of two adjacent LHCII trimers. In pea LCHII, three molecules of DGD occupy a hydrophobic cavity at the 3-fold axis of the complex. Recently, crystallization of the cyanobacterial PSII of Thermosynechococcus elong˚ resolution revealed that PSII contains several lipid molecules closely associated with the protein atus at 3.0 A complex [130]. Each PSII monomer binds four molecules of DGD, six MGD, three SQD and one PG. Eleven of these lipids surround the reaction center like a belt and three lipids are located at the monomer–monomer interface. This arrangement might confer flexibility for the local mobility of the subunits, thus facilitating the replacement of the D1 polypeptide during photodamage. Furthermore, different lipids were co-purified with PSII dimers from cyanobacteria and plants [131]. Presumably, specific protein–lipid interactions are also maintained in PSII complexes of higher plants. Furthermore, a large proportion of thylakoid lipids seem to be firmly bound to the periphery of photosynthetic complexes. Therefore, the number of freely diffusible lipid molecules in the bilayer membrane is rather small. Characterization of galactolipid-deficient Arabidopsis mutants revealed that a decrease in the proportion of MGD or DGD results in a reduction of chlorophyll content and photosynthetic activity, alterations in chloroplast ultrastructure, and an impairment of growth [14,17,132–134]. DGD plays an important role in the stability and activity of PSII and PSI [132–138]. Although DGD was so far not detected in cyanobacterial PSI (see above), nor in plant LCHI-PSI supercomplexes [135], the occurrence of DGD in PSI cannot be excluded at this point considering the fact that the current crystallographical resolution might not permit the identification of all lipids and co-factors. MGD was shown to be required for the activation of violaxanthin deepoxidase [139,140]. This enzyme which converts violaxanthin into antheraxanthin and zeaxanthin during the xanthophyll cycle plays an important role in photoprotection. However, the phospholipid PE, another, non-bilayer forming lipid, can also activate violaxanthin de-epoxidase demonstrating that enzyme activity depends on the presence of non-bilayer forming lipids rather than on specific galactolipid interactions [139,140]. The preference for the galactolipids in all organisms with oxygenic photosynthesis together with their identification in photosynthetic protein–pigment complexes (see above) suggests that galactolipids are crucial for photosynthesis. To address the role of the head group structure for photosynthetic activity, a transgenic approach was chosen which included the replacement of galactolipids in cyanobacteria and Arabidopsis with alternative glycolipids [13,141]. Thus, DGD was replaced with glucosylgalactosyldiacylglycerol by expression of a glucosyltransferase from C. aurantiacus in the Arabidopsis dgd1 mutant. The accumulation of glucosylgalactosyldiacylglycerol in the dgd1 mutant resulted in the complementation of growth deficiency. However, the decreases in chlorophyll content and in PSII quantum yield were only partially rescued, indicating that galactolipids represent the superior lipid class with regard to specific functional aspects of photosynthesis. 5. The role of galactolipids and other glycolipids during phosphate deprivation In many soils, phosphate deficiency is a limiting factor for growth of plants and microorganisms. To cope with this adverse condition, different adaptive strategies have evolved. Plants enhance their phosphate uptake capacity by altering root architecture. Arabidopsis for example responds to phosphate starvation with an increase in root and root hair formation accompanied with an inhibition of rosette growth [142]. Another adaptive strategy of saving phosphate is the redirection of metabolic pathways. In Arabidopsis, about onethird of organically bound phosphate is associated with phospholipids [143]. Plants are capable of substituting part of their membrane phospholipids with the two non-phosphorous lipids SQD and DGD. SQD and PG are required to maintain the anionic characteristics of the thylakoid membranes, and moreover, they play important roles in photosynthesis [144,145]. Extraplastidial PG, however, is not replaced by SQD [146].

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DGD which also accumulates under phosphate starvation in plants, replaces phospholipids in plastidial and extraplastidial membranes [142,147]. In oat exposed to phosphate deprivation, DGD was increased to up to 46% in the plasma membranes of shoot cells and up to 70% in plasma membranes of root cells [146]. Moreover, DGD was also detected in tonoplasts and in mitochondria [148,149]. The lipid transfer from the plastid to the mitochondria supposedly is mediated via physical contact zones between these two organelles [149]. The impact of DGD accumulation in extraplastidial compartments on different membrane-associated processes is unknown. It is believed that DGD as a neutral, bilayer forming lipid can replace several phospholipids, including PG, PC and PE. However, MGD and SQD were not detected outside of plastids [146–149]. Expression of type B MGDSs (Arabidopsis MGD2 and MGD3) is highly upregulated during phosphate deprivation [5], and depends on the regulation by the phytohormones auxin and cytokinin [150]. Presumably, MGD2 and MGD3 are involved in the synthesis of MGD which serves as precursor for DGD production during phosphate limitation. Furthermore, DGD1 and DGD2 which also show increased expression under phosphate deficiency [151], contribute to DGD synthesis under these conditions [8]. DGD was also identified as an abundant lipid in the peribacteroid membranes in the nodules of legumes [152]. Nitrogen-fixing Rhizobia proliferate inside the cytosol of plant root nodule cells where they are surrounded by a plant-derived, so-called peribacteroid membrane. This membrane contains DGD under phosphate deficient and under normal growth conditions, and it is believed that it replaces phospholipids during nodulation conditions when large amounts of membrane lipids are required for the production of the rhizobial and peribacteroid membranes. Similar to plants, the synthesis of SQD and DGD is stimulated during phosphate deprivation in cyanobacteria [25,26]. Regulation of lipid synthesis by phosphate deficiency and the role of the two anionic lipids, PG and SQD, in cyanobacteria has been reviewed by Frentzen [144] and Sato [145]. The impact of phosphate deficiency on membrane lipid composition under phosphate starvation in other bacteria has not been studied in detail. The anoxygenic photosynthetic bacterium Rhodobacter sphaeroides was shown to replace phospholipids with glycolipids during phosphate deprivation. SQD which is normally not important for growth and photosynthetic activity, serves as surrogate for PG during phosphate deprivation [50]. Furthermore, Rhodobacter accumulates high proportions of glucosylgalactosyldiacylglycerol (31%) (see above) and of betaine lipid (19%) [49]. These two lipids are not present under normal growth conditions. In Sinorhizobium meliloti, phospholipids constitute 95% of total lipids, the remainder being SQD and ornithine lipid. During phosphate limitation, phospholipids in Sinorhizobium are mainly replaced with betaine lipid [153]. In Brevundimonas diminuta, PG (as the only phospholipid), and a glycophospholipid are almost completely replaced with acidic glycolipids during phosphate starvation [154]. The moderate halophilic, Gram-positive bacteria Planococcus, Marinococcus and Salinicoccus contain high proportions of SQD, PG and low amounts of CL. In response to changes of salinity and phosphate availability, these organism alter the ratio of SQD to PG with mutual substitution of the two lipids [155]. The ability to substitute phospholipids with glycolipids is of high significance for marine ecosystems [156]. In the planktonic community of the North Pacific Subtropical Gyre, 18–28% of the phosphate assimilated is incorporated into membrane lipids. In contrast, Prochlorococcus, the dominating organism in the phytoplankton, uses less than 1% of phosphate taken up for phospholipid synthesis. These and other marine picocyanobacteria synthesize mainly SQD which together with MGD and DGD comprise about 94–99% of total lipids. The biochemical adaptation of employing sulfur instead of phosphorus for lipid synthesis confers an ecological advantage for picocyanobacteria in the competition for phosphate with phospholipid-rich heterotrophic bacteria in phosphate-depleted marine environments. 6. Conclusions Chloroplasts and cyanobacteria are characterized by a conserved set of glycerolipids in their thylakoid membranes. Research in the past has provided detailed insight into galactolipid synthesis in plants, including the localization and function of the relevant enzymes. Our understanding of galactolipid synthesis in cyanobacteria, however, is still incomplete because the genes coding for cyanobacterial epimerase and DGDS remain unknown. The mechanisms of lipid trafficking within chloroplasts and bacteria, and between different organelles of the plant cell are not understood and will be the focus of future research. Bacteria provide diverse sources for novel glycoglycerolipids with different head group structures. However, only a few genes involved in bacterial glycoglycerolipid synthesis have been isolated. Furthermore, the function of bacterial glycolipids is

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only partially understood. Glycolipids affect the function and activity of proteins in membranes, as was shown for galactolipid interaction with photosynthetic protein complexes in plants and cyanobacteria. Furthermore, glycolipids are crucial for membrane bilayer characteristics and for the stability of protein complexes, and they play an essential role during phosphate limitation in plants and bacteria by replacing phospholipids and thus facilitating the survival in phosphate-limited environments. Acknowledgements We thank Prof. Ernst Heinz (University of Hamburg, Germany) for critically reading the manuscript. This work was in part supported by the Deutsche Forschungsgemeinschaft (Grant Ho3870/1) and by the Max Planck Society. References [1] Siegenthaler P. Molecular organization of acyl lipids in photosynthetic membranes of higher plants. In: Siegenthaler P, Murata N, editors. Lipids in photosynthesis: structure, function and genetics. 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