A microbial factory for defensive kahalalides in a tripartite marine symbiosis

Zan, Jindong; Li, Zhiyuan; Tianero, Ma. Diarey B.; Davis, Jeanette; Hill, Russell T.; Donia, Mohamed S.

doi:10.1126/science.aaw6732

Cited by 87 publications

(80 citation statements)

References 57 publications

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“…A nimals are rich sources of complex polyketides, yet most polyketides are made by microbes [1][2][3] . Polyketides isolated from animals are sometimes produced by symbiotic bacteria or dietary organisms and not by the animals themselves 4,5 . However, because of these data, it is often claimed that complex natural products such as polyketides must be made by symbiotic bacteria, despite a lack of evidence for most compounds found in nature.…”

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confidence: 99%

Animal biosynthesis of complex polyketides in a photosynthetic partnership

et al. 2020

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Complex polyketides are typically associated with microbial metabolism. Here, we report that animals also make complex, microbe-like polyketides. We show there is a widespread branch of fatty acid synthase-(FAS)-like polyketide synthase (PKS) proteins, which sacoglossan animals use to synthesize complex products. The purified sacogolassan protein EcPKS1 uses only methylmalonyl-CoA as a substrate, otherwise unknown in animal lipid metabolism. Sacoglossans are sea slugs, some of which eat algae, digesting the cells but maintaining functional chloroplasts. Here, we provide evidence that polyketides support this unusual photosynthetic partnership. The FAS-like PKS family represents an uncharacterized branch of polyketide and fatty acid metabolism, encoding a large diversity of biomedically relevant animal enzymes and chemicals awaiting discovery. The biochemical characterization of an intact animal polyketide biosynthetic enzyme opens the door to understanding the immense untapped metabolic potential of metazoans.

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confidence: 99%

Animal biosynthesis of complex polyketides in a photosynthetic partnership

et al. 2020

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“…Bioactive compounds produced by symbiotic bacteria often play a role in chemical defense for the host, as demonstrated in several species of bryozoans [29], sponges [30], molluscs [31], and ascidians [32]. In some cases, symbiotically produced defense compounds are acquired and sequestered by specialized predators, as recently described in the sea slug Elysia rufescens, which acquires microbial symbiotically produced kahalalide toxins from its algal prey Bryopsis [33].…”

Section: How Microbial Symbiosis Impacts Marine Ecosystem Functioningmentioning

confidence: 95%

Host-associated microbiomes and their roles in marine ecosystem functions

Wilkins

Leray

Yuen

et al. 2019

Preprint

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The significance of mutualisms between eukaryotic hosts and microbes extends from the organismal to the ecosystem level, and mutualistic symbioses underpin the health of Earth’s most threatened marine ecosystems. Despite rapid growth in research on host-associated microbes (microbiomes), very little is known about their interactions for the vast majority of marine host species. We outline research priorities to broaden our current knowledge of host-microbiome interactions and how they shape marine ecosystems. We argue that this research frontier will allow us to predict responses of species, communities, and ecosystems to stressors driven by human activity, and inform future management and mitigation.

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“…12 Some depsipeptides are involved in microbial pathogenesis, like the emetic toxin cereulide. 110 Depsipeptides have a variety of natural functions, from increasing organism fitness in K + deprived environments 14 to participating in symbiotic relationships both in marine 111 and terrestrial 18,112 organisms. Among the most interesting examples in symbiosis is the role of depsipeptides in the relationships between microorganisms and ants: Actinomycin, valinomycin, and antimycin participate in a tripartite symbiotic relationship between Streptomyces sp., a fungus, and leaf-cutter ants, 18,112 while dentigerumycin made in Pseudonocardia actinobacteria helps control pathogenic fungal growth in fungal gardens cultivated by ants.…”

Section: Introduction To Nonribosomal Peptide Synthetases and Theirmentioning

confidence: 99%

Biosynthesis of depsipeptides, or Depsi: The peptides with varied generations

Alonzo

Schmeing

2020

Protein Science

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Depsipeptides are compounds that contain both ester bonds and amide bonds. Important natural product depsipeptides include the piscicide antimycin, the K + ionophores cereulide and valinomycin, the anticancer agent cryptophycin, and the antimicrobial kutzneride. Furthermore, database searches return hundreds of uncharacterized systems likely to produce novel depsipeptides. These compounds are made by specialized nonribosomal peptide synthetases (NRPSs). NRPSs are biosynthetic megaenzymes that use a module architecture and multi-step catalytic cycle to assemble monomer substrates into peptides, or in the case of specialized depsipeptide synthetases, depsipeptides. Two NRPS domains, the condensation domain and the thioesterase domain, catalyze ester bond formation, and ester bonds are introduced into depsipeptides in several different ways. The two most common occur during cyclization, in a reaction between a hydroxy-containing side chain and the C-terminal amino acid residue in a peptide intermediate, and during incorporation into the growing peptide chain of an α-hydroxy acyl moiety, recruited either by direct selection of an α-hydroxy acid substrate or by selection of an α-keto acid substrate that is reduced in situ. In this article, we discuss how and when these esters are introduced during depsipeptide synthesis, survey notable depsipeptide synthetases, and review insight into bacterial depsipeptide synthetases recently gained from structural studies.

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A microbial factory for defensive kahalalides in a tripartite marine symbiosis

Cited by 87 publications

References 57 publications

Animal biosynthesis of complex polyketides in a photosynthetic partnership

Animal biosynthesis of complex polyketides in a photosynthetic partnership

Host-associated microbiomes and their roles in marine ecosystem functions

Biosynthesis of depsipeptides, or Depsi: The peptides with varied generations

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