- Email: [email protected]
Evolution of metabolic diversity
Phytochemistry 70 (2009) 1619–1620
Contents lists available at ScienceDirect
Phytochemistry journal homepage: www.elsevier.com/locate/phytochem
Editorial
Evolution of metabolic diversity
Living organisms produce a diverse array of metabolites that are generally not involved in the basic processes of growth and development. We call these compounds secondary metabolites. Plants and microorganism, in particular, are characterized by an extremely diverse and multifaceted secondary metabolism. For example, in plants these secondary metabolites determine our sensory perception of unique characteristics: we see their characteristic colors and smell the fragrances of flowers and fruits, and appreciate the distinctive tastes of spices, vegetables, and fruits. Moreover, almost all of the biological activities of plants and microorganisms that humans have used for medicinal purposes for hundreds of years can be attributed to secondary metabolites. The best known secondary metabolites of microorganisms are, besides the disastrous toxins, the various classes of antibiotics successfully applied in medicine to combat infectious diseases. Secondary metabolism plays an essential role in the interactions of the producing organism with its abiotic and biotic environment. Secondary metabolites may protect plants against attack by herbivores and pathogens because of their toxic, irritating, deterrent or antimicrobial properties. Among microbes, although less intensively studied, antibiotics and other toxins are probably beneficial for the producer in food competition and defense against unicellular eukaryotes. Furthermore, recent findings support the concept that secondary metabolites also serve the communication between microorganisms and all other organisms. The idea that the components of secondary metabolism evolved under the selection pressure of the environment is now broadly accepted among biologists. In this evolutionary context the immense diversity of plant and microbial secondary products represents an essential part of these organisms’ strategies to cope with the adversities of their environment. For example, each plant species possesses its distinctive endowment of secondary metabolites well adapted to the particular demands of the plants environment. The diversity of secondary metabolism simply reflects the diversity of plants and microorganisms, each adapted in time and space to its specific ecological niche. When we analyze the secondary chemistry of a given population we evaluate its current state that resulted from a dynamic long-lasting evolutionary process. This process may cover millions of years of evolution and speciation that follows from successful adaptations to the changing biotic and abiotic environmental conditions. All in all secondary metabolism constitutes the chemical facet of biodiversity. This dynamic scenario of secondary metabolism provides a fascinating basis for establishing the molecular mechanism behind the microevolutionary events of secondary metabolism and it continuous adaptations to environmental demands. In 2003, the Deut0031-9422/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2009.07.007
sche Forschungsgemeinschaft (DFG, German Research Foundation) established the Priority Program SPP 1152 ‘‘evolution of metabolic diversity” (EvoMet) to promote collaboration between plant scientists, microbiologists and biochemists, with the mutual aim of investigating the evolutionary basis of the diversity of secondary product formation in plants, fungi and bacteria. It was clear from the very beginning that the project could not be efficiently addressed by selecting model organisms. The various aspects and strategies of the evolution of secondary pathways could only be mastered by comparing different plant and microbial systems. Key questions were addressed on three mechanistic levels: (i) the gene level, (ii) the protein (enzyme) level and (iii) the product (metabolite) level. Any substantial hypothesis about evolutionary mechanisms that are eminent for the generation of natural product diversity relies on the elucidation of the genetic basis and the in-depth biochemical analysis of the biosynthetic enzymes and a complete resolution and identification of the final products. The SPP 1152 pursued individual projects covering research within these three levels. On the gene level projects identify gene duplications and recruitment of the duplicates for establishing new functions (neo-functionalization) as major mechanisms for pathway evolution (e.g., benzoxazinoids, pyrrolizidines, glucosinolates, ß-lactams and phosphinothricin). Both mechanisms are required to establish branching points from primary metabolism and are necessary for the diversification of genes encoding modifying enzymes. Functional diversification at the enzyme level was the major theme in a number of studies concerning, among others, glycosyltransferases, acyltransferases, prenyltransferases, terpene synthases and polyketide synthases. In several of these studies, the requirements for changing catalytic properties were mechanistically addressed by combining molecular, biochemical approaches and structural chemistry under evolutionary considerations. In microbes the complete sets of enzymes catalyzing individual biosynthetic pathways are encoded by organized gene clusters. From the evolutionary and biotechnological point of view rearrangements by gene swapping between different clusters appear to represent a common way for functional diversification. The collaboration of plant biologists and microbiologists, two disciplines that usually go their own ways, turned out to be more inspiring than expected by both groups at the beginning. There was not only an exchange of common technologies but also common ideas and suggestions, in particular those concerning polyketides, structural work and the emerging evidence that biosynthetic genes are often also clustered in plant genomes. Moreover, several topics are related to evolutionary aspects of classes of secondary
1620
Editorial / Phytochemistry 70 (2009) 1619–1620
metabolites that occur in plants and microbes (camalexin, gibberellins) or are related to parasitic or mutualistic interactions between organisms (ergot alkaloids and sponge-bacteria polyketides). This Special Issue of Phytochemistry presents a collection of individual reviews, that summarize the major results obtained within the Priority Program during six years financial support by the DFG. The manuscripts focus on the authors own results, which are discussed in the context of the international state of knowledge in the field. Two invited experts from Japan (Kazuki Saito and Kazufumi Yazaki), who actively participated in the final symposium of the program, complete the collection. All groups supported within the Priority Program EvoMet greatly acknowledge the support by the DFG, which provided the basis for the success of this program. The groups would also like to thank all reviewers of the program for critical and constructive examination of the research projects. We hope that this Special Issue, apart from its importance as a major result of the Priority Program, will encourage future research and collaborations in the fascinating field of modern natural product biology. Guest Editors Axel Brakhage Leibniz Institut für Naturstoff-Forschung und Infektionsbiologie, Abteilung Molekulare und Angewandte Mikrobiologie, Beutenbergstraße 11a, D-07745 Jena, Germany E-mail address: [email protected]
Alfons Gierl Technische Universität München, Wissenschaftszentrum Weihenstephan, Am Hochanger 8, D-85354 Freising, Germany E-mail address: [email protected] Thomas Hartmann Technische Universität Braunschweig, Institut für Pharmazeutische Biologie, Mendelssohnstr. 1, D-38106 Braunschweig, Germany E-mail address: [email protected] Editor Dieter Strack Leibniz Institut für Pflanzenbiochemie, Abteilung Sekundärstoffwechsel, Weinberg 3, D-06120 Halle (Saale), Germany E-mail address: [email protected] Available online 6 August 2009
Contents lists available at ScienceDirect
Phytochemistry journal homepage: www.elsevier.com/locate/phytochem
Editorial
Evolution of metabolic diversity
Living organisms produce a diverse array of metabolites that are generally not involved in the basic processes of growth and development. We call these compounds secondary metabolites. Plants and microorganism, in particular, are characterized by an extremely diverse and multifaceted secondary metabolism. For example, in plants these secondary metabolites determine our sensory perception of unique characteristics: we see their characteristic colors and smell the fragrances of flowers and fruits, and appreciate the distinctive tastes of spices, vegetables, and fruits. Moreover, almost all of the biological activities of plants and microorganisms that humans have used for medicinal purposes for hundreds of years can be attributed to secondary metabolites. The best known secondary metabolites of microorganisms are, besides the disastrous toxins, the various classes of antibiotics successfully applied in medicine to combat infectious diseases. Secondary metabolism plays an essential role in the interactions of the producing organism with its abiotic and biotic environment. Secondary metabolites may protect plants against attack by herbivores and pathogens because of their toxic, irritating, deterrent or antimicrobial properties. Among microbes, although less intensively studied, antibiotics and other toxins are probably beneficial for the producer in food competition and defense against unicellular eukaryotes. Furthermore, recent findings support the concept that secondary metabolites also serve the communication between microorganisms and all other organisms. The idea that the components of secondary metabolism evolved under the selection pressure of the environment is now broadly accepted among biologists. In this evolutionary context the immense diversity of plant and microbial secondary products represents an essential part of these organisms’ strategies to cope with the adversities of their environment. For example, each plant species possesses its distinctive endowment of secondary metabolites well adapted to the particular demands of the plants environment. The diversity of secondary metabolism simply reflects the diversity of plants and microorganisms, each adapted in time and space to its specific ecological niche. When we analyze the secondary chemistry of a given population we evaluate its current state that resulted from a dynamic long-lasting evolutionary process. This process may cover millions of years of evolution and speciation that follows from successful adaptations to the changing biotic and abiotic environmental conditions. All in all secondary metabolism constitutes the chemical facet of biodiversity. This dynamic scenario of secondary metabolism provides a fascinating basis for establishing the molecular mechanism behind the microevolutionary events of secondary metabolism and it continuous adaptations to environmental demands. In 2003, the Deut0031-9422/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2009.07.007
sche Forschungsgemeinschaft (DFG, German Research Foundation) established the Priority Program SPP 1152 ‘‘evolution of metabolic diversity” (EvoMet) to promote collaboration between plant scientists, microbiologists and biochemists, with the mutual aim of investigating the evolutionary basis of the diversity of secondary product formation in plants, fungi and bacteria. It was clear from the very beginning that the project could not be efficiently addressed by selecting model organisms. The various aspects and strategies of the evolution of secondary pathways could only be mastered by comparing different plant and microbial systems. Key questions were addressed on three mechanistic levels: (i) the gene level, (ii) the protein (enzyme) level and (iii) the product (metabolite) level. Any substantial hypothesis about evolutionary mechanisms that are eminent for the generation of natural product diversity relies on the elucidation of the genetic basis and the in-depth biochemical analysis of the biosynthetic enzymes and a complete resolution and identification of the final products. The SPP 1152 pursued individual projects covering research within these three levels. On the gene level projects identify gene duplications and recruitment of the duplicates for establishing new functions (neo-functionalization) as major mechanisms for pathway evolution (e.g., benzoxazinoids, pyrrolizidines, glucosinolates, ß-lactams and phosphinothricin). Both mechanisms are required to establish branching points from primary metabolism and are necessary for the diversification of genes encoding modifying enzymes. Functional diversification at the enzyme level was the major theme in a number of studies concerning, among others, glycosyltransferases, acyltransferases, prenyltransferases, terpene synthases and polyketide synthases. In several of these studies, the requirements for changing catalytic properties were mechanistically addressed by combining molecular, biochemical approaches and structural chemistry under evolutionary considerations. In microbes the complete sets of enzymes catalyzing individual biosynthetic pathways are encoded by organized gene clusters. From the evolutionary and biotechnological point of view rearrangements by gene swapping between different clusters appear to represent a common way for functional diversification. The collaboration of plant biologists and microbiologists, two disciplines that usually go their own ways, turned out to be more inspiring than expected by both groups at the beginning. There was not only an exchange of common technologies but also common ideas and suggestions, in particular those concerning polyketides, structural work and the emerging evidence that biosynthetic genes are often also clustered in plant genomes. Moreover, several topics are related to evolutionary aspects of classes of secondary
1620
Editorial / Phytochemistry 70 (2009) 1619–1620
metabolites that occur in plants and microbes (camalexin, gibberellins) or are related to parasitic or mutualistic interactions between organisms (ergot alkaloids and sponge-bacteria polyketides). This Special Issue of Phytochemistry presents a collection of individual reviews, that summarize the major results obtained within the Priority Program during six years financial support by the DFG. The manuscripts focus on the authors own results, which are discussed in the context of the international state of knowledge in the field. Two invited experts from Japan (Kazuki Saito and Kazufumi Yazaki), who actively participated in the final symposium of the program, complete the collection. All groups supported within the Priority Program EvoMet greatly acknowledge the support by the DFG, which provided the basis for the success of this program. The groups would also like to thank all reviewers of the program for critical and constructive examination of the research projects. We hope that this Special Issue, apart from its importance as a major result of the Priority Program, will encourage future research and collaborations in the fascinating field of modern natural product biology. Guest Editors Axel Brakhage Leibniz Institut für Naturstoff-Forschung und Infektionsbiologie, Abteilung Molekulare und Angewandte Mikrobiologie, Beutenbergstraße 11a, D-07745 Jena, Germany E-mail address: [email protected]
Alfons Gierl Technische Universität München, Wissenschaftszentrum Weihenstephan, Am Hochanger 8, D-85354 Freising, Germany E-mail address: [email protected] Thomas Hartmann Technische Universität Braunschweig, Institut für Pharmazeutische Biologie, Mendelssohnstr. 1, D-38106 Braunschweig, Germany E-mail address: [email protected] Editor Dieter Strack Leibniz Institut für Pflanzenbiochemie, Abteilung Sekundärstoffwechsel, Weinberg 3, D-06120 Halle (Saale), Germany E-mail address: [email protected] Available online 6 August 2009