Evolutionary Implications of Bacterial Polyketide Synthases

Jenke‐Kodama, Holger; Sandmann, Axel; Müller, Rolf; Dittmann, Elke

doi:10.1093/molbev/msi193

Cited by 328 publications

(325 citation statements)

References 51 publications

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“…1B; SI Appendix, Table S3). Although trans-AT PKS systems have been found in a wide range of bacteria (16,17), none have been reported for cyanobacteria, which are otherwise rich sources of cis-AT PKSs (17,18). These observations suggested the possibility of metabolic products that might be novel, not only from structural but also from ecological and evolutionary perspectives.…”

Section: Resultsmentioning

confidence: 99%

Metagenomic natural product discovery in lichen provides evidence for a family of biosynthetic pathways in diverse symbioses

Kampa

Gagunashvili

Gulder

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

126

127

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Bacteria are a major source of natural products that provide rich opportunities for both chemical and biological investigation. Although the vast majority of known bacterial metabolites derive from free-living organisms, increasing evidence supports the widespread existence of chemically prolific bacteria living in symbioses. A strategy based on bioinformatic prediction, symbiont cultivation, isotopic enrichment, and advanced analytics was used to characterize a unique polyketide, nosperin, from a lichen-associated Nostoc sp. cyanobacterium. The biosynthetic gene cluster and the structure of nosperin, determined from 30 μg of compound, are related to those of the pederin group previously known only from nonphotosynthetic bacteria associated with beetles and marine sponges. The presence of this natural product family in such highly dissimilar associations suggests that some bacterial metabolites may be specific to symbioses with eukaryotes and encourages exploration of other symbioses for drug discovery and better understanding of ecological interactions mediated by complex bacterial metabolites.biosynthesis | Peltigera membranacea | trans-acyltransferase polyketide synthase | 13 C nuclear magnetic resonance

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Section: Resultsmentioning

confidence: 99%

Metagenomic natural product discovery in lichen provides evidence for a family of biosynthetic pathways in diverse symbioses

Kampa

Gagunashvili

Gulder

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

126

127

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“…S2), resulting in two new insights into the nature and timing of this duplication in the context of bacterial evolution. First, type II PKS KSs appear more similar to primary metabolic FabF KS homologs from the fatty acid (FAS) pathway than to the KS of several secondary metabolic type II PKS relatives, such as aurachin and kedarcidin (1,3,4,(16)(17)(18). These other secondary metabolic gene clusters harbor tandem KSs that appear superficially similar to the tandem KSs of type II PKS gene clusters (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Elucidating the history of how gene clusters evolved to produce a powerhouse of structurally diverse and biologically active molecules could reveal how synthases can be engineered to produce new therapeutic agents. Phylogenetic analyses have revealed evolutionary histories of individual biosynthetic genes, but the mechanisms of evolution of entire gene clusters are not well understood (1)(2)(3)(4).…”

mentioning

confidence: 99%

Evolution of chemical diversity by coordinated gene swaps in type II polyketide gene clusters

Hillenmeyer

Vandova

Berlew

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Natural product biosynthetic pathways generate molecules of enormous structural complexity and exquisitely tuned biological activities. Studies of natural products have led to the discovery of many pharmaceutical agents, particularly antibiotics. Attempts to harness the catalytic prowess of biosynthetic enzyme systems, for both compound discovery and engineering, have been limited by a poor understanding of the evolution of the underlying gene clusters. We developed an approach to study the evolution of biosynthetic genes on a cluster-wide scale, integrating pairwise gene coevolution information with large-scale phylogenetic analysis. We used this method to infer the evolution of type II polyketide gene clusters, tracing the path of evolution from the single ancestor to those gene clusters surviving today. We identified 10 key gene types in these clusters, most of which were swapped in from existing cellular processes and subsequently specialized. The ancestral type II polyketide gene cluster likely comprised a core set of five genes, a roster that expanded and contracted throughout evolution. A key C24 ancestor diversified into major classes of longer and shorter chain length systems, from which a C20 ancestor gave rise to the majority of characterized type II polyketide antibiotics. Our findings reveal that (i) type II polyketide structure is predictable from its gene roster, (ii) only certain gene combinations are compatible, and (iii) gene swaps were likely a key to evolution of chemical diversity. The lessons learned about how natural selection drives polyketide chemical innovation can be applied to the rational design and guided discovery of chemicals with desired structures and properties.evolution | polyketide | natural products | gene cluster

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“…In contrast to the traditional desaturase-based PUFA biosynthesis pathway, M. marina MP-1 uses a distinct polyketide synthase (PKS)-type pathway that remains poorly characterized (Jenke-Kodama et al 2005;Metz et al 2001;Napier 2002). PKS-type pathways are important for a variety of complex natural products, such as cholesterol-lowering lovastatins (Campbell and Vederas), among others (Busch and Hertweck 2009;Calderone 2008;Shen 2003).…”

Section: Introductionmentioning

confidence: 99%

Growth condition optimization for docosahexaenoic acid (DHA) production by Moritella marina MP-1

Kautharapu

Rathmacher

Jarboe

2012

Appl Microbiol Biotechnol

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The marine organism Moritella marina MP-1 produces the polyunsaturated fatty acid docosahexaenoic acid (DHA). While the basic metabolic pathway for DHA production in this organism has been identified, the impact of growth conditions on DHA production is largely unknown. This study examines the effect of supplemental carbon, nitrogen and salts, growth temperature and media composition and pH on DHA and biomass production and the fatty acid profile. The addition of supplemental nitrogen significantly increased the overall DHA titer via an increase in biomass production. Supplemental glucose or glycerol increased biomass production, but decreased the amount of DHA per biomass, resulting in no net change in the DHA titer. Acidification of the baseline media pH to 6.0 increased DHA per biomass. Changes in growth temperature or provision of supplemental sodium or magnesium chloride did not increase DHA titer. This organism was also shown to grow on defined minimal media. For both media types, glycerol enabled more DHA production per biomass than glucose. Combination of these growth findings into marine broth supplemented with glycerol, yeast extract, and tryptone at pH 6.0 resulted in a final titer of 82 Â± 5 mg/L, a nearly eightfold increase relative to the titer of 11 Â± 1 mg/L seen in the unsupplemented marine broth. The relative distribution of other fatty acids was relatively robust to growth condition, but the presence of glycerol resulted in a significant increase in myristic acid (C14:0) and decrease in palmitic acid (C16:0). In summary, DHA production by M. marina MP-1 can be increased more than fivefold by changing the growth media. Metabolic engineering of this organism to increase the amount of DHA produced per biomass could result in additional increases in titer. ABSTRACTThe marine organism Moritella marina MP-1 produces the polyunsaturated fatty acid docosahexaenoic acid (DHA). While the basic metabolic pathway for DHA production in this organism has been identified, the impact of growth conditions on DHA production is largely unknown. This study examines the effect of supplemental carbon, nitrogen and salts, growth temperature and media composition and pH on DHA and biomass production and the fatty acid profile. The addition of supplemental nitrogen significantly increased the overall DHA titer via an increase in biomass production. Supplemental glucose or glycerol increased biomass production, but decreased the amount of DHA per biomass, resulting in no net change in the DHA titer.Acidification of the baseline media pH to 6.0 increased DHA per biomass. Changes in growth temperature or provision of supplemental sodium or magnesium chloride did not increase DHA titer. This organism was also shown to grow on defined minimal media. For both media types, glycerol enabled more DHA production per biomass than glucose. Combination of these growth findings into marine broth supplemented with glycerol, yeast extract and tryptone at pH 6.0 resulted in a final titer of 82+5 mg/L, a nearly 8-fold increase...

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Evolutionary Implications of Bacterial Polyketide Synthases

Cited by 328 publications

References 51 publications

Metagenomic natural product discovery in lichen provides evidence for a family of biosynthetic pathways in diverse symbioses

Metagenomic natural product discovery in lichen provides evidence for a family of biosynthetic pathways in diverse symbioses

Evolution of chemical diversity by coordinated gene swaps in type II polyketide gene clusters

Growth condition optimization for docosahexaenoic acid (DHA) production by Moritella marina MP-1

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