Origin and Variation of Tunicate Secondary Metabolites

Schmidt, Eric W.; Donia, Mohamed S.; McIntosh, Jason S.; Fricke, W. Florian; Ravel, Jacques

doi:10.1021/np200665k

Cited by 76 publications

(66 citation statements)

References 66 publications

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“…Similar to prochlorosins, some cyanobactin variants arise from duplication and diversification events in their precursor peptide genes (32). However, in contrast to prochlorosins, natural genetic variation patterns found in precursor peptides of the patellamide family of cyanobactins from tunicate-associated cyanobacteria suggest that their evolutionary diversification occurs through small stepwise changes, somewhat constrained by the maintenance of conserved residues and the overall length of the peptide (33). Not all families of cyanobactins, however, display marked similarities between closely related variants of precursor peptide genes.…”

Section: Hypervariability Of Prochlorosin Structures In Wild Populatimentioning

confidence: 99%

Evolutionary radiation of lanthipeptides in marine cyanobacteria

Cubillos-Ruiz

Berta-Thompson

Becker

et al. 2017

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

114

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Lanthipeptides are ribosomally derived peptide secondary metabolites that undergo extensive posttranslational modification. Prochlorosins are a group of lanthipeptides produced by certain strains of the ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Unlike other lanthipeptide-producing bacteria, picocyanobacteria use an unprecedented mechanism of substrate promiscuity for the production of numerous and diverse lanthipeptides using a single lanthionine synthetase. Through a cross-scale analysis of prochlorosin biosynthesis genes-from genomes to oceanic populations-we show that marine picocyanobacteria have the collective capacity to encode thousands of different cyclic peptides, few of which would display similar ring topologies. To understand how this extensive structural diversity arises, we used deep sequencing of wild populations to reveal genetic variation patterns in prochlorosin genes. We present evidence that structural variability among prochlorosins is the result of a diversifying selection process that favors large, rather than small, sequence changes in the precursor peptide genes. This mode of molecular evolution disregards any conservation of the ancestral structure and enables the emergence of extensively different cyclic peptides through short mutational paths based on indels. Contrary to its fast-evolving peptide substrates, the prochlorosin lanthionine synthetase evolves under a strong purifying selection, indicating that the diversification of prochlorosins is not constrained by commensurate changes in the biosynthetic enzyme. This evolutionary interplay between the prochlorosin peptide substrates and the lanthionine synthetase suggests that structure diversification, rather than structure refinement, is the driving force behind the creation of new prochlorosin structures and represents an intriguing mechanism by which natural product diversity arises.icrobial secondary metabolism produces a wealth of small molecules, referred to as natural products. These metabolites are fundamental for the function of microbial communities because they play diverse roles in mediating both biotic and abiotic interactions (1, 2). Studies on the diversity of secondary metabolite biosynthetic pathways in the human gut (3), soil (4), and marine sediments (5) indicate that the production of structurally diverse natural products is an integral feature of microbial communities. The oligotrophic ocean is the largest ecosystem on Earth, yet little is known about secondary metabolite production in planktonic marine microbial communities in part because their dilute habitat presents an unconventional stage for the action of these types of often-secreted compounds.A survey of secondary metabolite pathways in sequenced genomes of Prochlorococcus and Synechococcus, the most abundant phytoplankton groups in the ocean, revealed the presence of a lanthipeptide biosynthesis pathway (6). The compounds produced by this pathway were named prochlorosins and are the first natural products identified in marine...

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Section: Hypervariability Of Prochlorosin Structures In Wild Populatimentioning

confidence: 99%

Evolutionary radiation of lanthipeptides in marine cyanobacteria

Cubillos-Ruiz

Berta-Thompson

Becker

et al. 2017

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

114

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“…Filter-feeding chordates known as ascidians are found in all of the world's oceans (Shenkar and Swalla, 2011;Schmidt et al, 2012). Ascidians are sessile, soft-bodied animals that are vulnerable to predation.…”

Section: Introductionmentioning

confidence: 99%

Species specificity of symbiosis and secondary metabolism in ascidians

et al. 2014

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Ascidians contain abundant, diverse secondary metabolites, which are thought to serve a defensive role and which have been applied to drug discovery. It is known that bacteria in symbiosis with ascidians produce several of these metabolites, but very little is known about factors governing these 'chemical symbioses'. To examine this phenomenon across a wide geographical and species scale, we performed bacterial and chemical analyses of 32 different ascidians, mostly from the didemnid family from Florida, Southern California and a broad expanse of the tropical Pacific Ocean. Bacterial diversity analysis showed that ascidian microbiomes are highly diverse, and this diversity does not correlate with geographical location or latitude. Within a subset of species, ascidian microbiomes are also stable over time (R ¼ À 0.037, P-value ¼ 0.499). Ascidian microbiomes and metabolomes contain species-specific and location-specific components. Location-specific bacteria are found in low abundance in the ascidians and mostly represent strains that are widespread. Location-specific metabolites consist largely of lipids, which may reflect differences in water temperature. By contrast, species-specific bacteria are mostly abundant sequenced components of the microbiomes and include secondary metabolite producers as major components. Species-specific chemicals are dominated by secondary metabolites. Together with previous analyses that focused on single ascidian species or symbiont type, these results reveal fundamental properties of secondary metabolic symbiosis. Different ascidian species have established associations with many different bacterial symbionts, including those known to produce toxic chemicals. This implies a strong selection for this property and the independent origin of secondary metabolite-based associations in different ascidian species. The analysis here streamlines the connection of secondary metabolite to producing bacterium, enabling further biological and biotechnological studies.

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“…1 A and B), is a promising model for studying the importance of secondary metabolites in symbiosis. Like other tunicates, L. patella is a rich source of potentially bioactive drugs and drug leads (11), which in a few cases are known to be produced by symbiotic bacteria (7,8). Beyond the major symbiont, the cyanobacterium Prochloron didemni, L. patella harbors a complex microbiome (12).…”

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confidence: 99%

Genome streamlining and chemical defense in a coral reef symbiosis

Kwan

Donia

Han

et al. 2012

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

Self Cite

142

206

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Secondary metabolites are ubiquitous in bacteria, but by definition, they are thought to be nonessential. Highly toxic secondary metabolites such as patellazoles have been isolated from marine tunicates, where their exceptional potency and abundance implies a role in chemical defense, but their biological source is unknown. Here, we describe the association of the tunicate Lissoclinum patella with a symbiotic α-proteobacterium, Candidatus Endolissoclinum faulkneri, and present chemical and biological evidence that the bacterium synthesizes patellazoles. We sequenced and assembled the complete Ca. E. faulkneri genome, directly from metagenomic DNA obtained from the tunicate, where it accounted for 0.6% of sequence data. We show that the large patellazoles biosynthetic pathway is maintained, whereas the remainder of the genome is undergoing extensive streamlining to eliminate unneeded genes. The preservation of this pathway in streamlined bacteria demonstrates that secondary metabolism is an essential component of the symbiotic interaction.ascidian | trans-acyltransferase | natural products | polyketide | biosynthesis

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Origin and Variation of Tunicate Secondary Metabolites

Cited by 76 publications

References 66 publications

Evolutionary radiation of lanthipeptides in marine cyanobacteria

Evolutionary radiation of lanthipeptides in marine cyanobacteria

Species specificity of symbiosis and secondary metabolism in ascidians

Genome streamlining and chemical defense in a coral reef symbiosis

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