Natural product discovery from the human microbiome

Wilson, Michael; Zha, Li; Balskus, Emily P.

doi:10.1074/jbc.r116.762906

Cited by 69 publications

(42 citation statements)

References 72 publications

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“…symbiosis | natural products | biosynthesis | microbiomes | sponges T here is strong evidence that microbiome-derived specialized metabolites play key roles in health, disease, reproductive success, evolutive diversification, and the survival of macroorganisms (1,2). An important example is defensive symbiosis in which hosts benefit from protective substances synthesized by a microbial partner (3).…”

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confidence: 99%

A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli

Rust

Helfrich

Freeman

et al. 2020

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

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Bacterial specialized metabolites are increasingly recognized as important factors in animal–microbiome interactions: for example, by providing the host with chemical defenses. Even in chemically rich animals, such compounds have been found to originate from individual members of more diverse microbiomes. Here, we identified a remarkable case of a moderately complex microbiome in the sponge host Mycale hentscheli in which multiple symbionts jointly generate chemical diversity. In addition to bacterial pathways for three distinct polyketide families comprising microtubule-inhibiting peloruside drug candidates, mycalamide-type contact poisons, and the eukaryotic translation-inhibiting pateamines, we identified extensive biosynthetic potential distributed among a broad phylogenetic range of bacteria. Biochemical data on one of the orphan pathways suggest a previously unknown member of the rare polytheonamide-type cytotoxin family as its product. Other than supporting a scenario of cooperative symbiosis based on bacterial metabolites, the data provide a rationale for the chemical variability of M. hentscheli and could pave the way toward biotechnological peloruside production. Most bacterial lineages in the compositionally unusual sponge microbiome were not known to synthesize bioactive metabolites, supporting the concept that microbial dark matter harbors diverse producer taxa with as yet unrecognized drug discovery potential.

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mentioning

confidence: 99%

A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli

Rust

Helfrich

Freeman

et al. 2020

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

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“…Secondary metabolism is one of the most diverse features of microbial communities [90,91]. A wide range of small molecule metabolites are synthesized by microorganisms as a representation of metabolic complexity [92,93]. Being essential tool for self-defense, they play major role in host-microbe, microbe-microbe, and microbe-environment interactions [94] and act as clinically-used antibiotics, antimicrobials, anticancer agents, immuno-suppressants, and other drugs [93,95].…”

Section: Secondary Metabolismmentioning

confidence: 99%

Rhizosphere Metagenomics of Paspalum scrobiculatum L. (Kodo Millet) Reveals Rhizobiome Multifunctionalities

et al. 2019

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Multifunctionalities linked with the microbial communities associated with the millet crop rhizosphere has remained unexplored. In this study, we are analyzing microbial communities inhabiting rhizosphere of kodo millet and their associated functions and its impact over plant growth and survival. Metagenomics of Paspalum scrobiculatum L.(kodo millet) rhizopshere revealed taxonomic communities with functional capabilities linked to support growth and development of the plants under nutrient-deprived, semi-arid and dry biotic conditions. Among 65 taxonomically diverse phyla identified in the rhizobiome, Actinobacteria were the most abundant followed by the Proteobacteria. Functions identified for different genes/proteins led to revelations that multifunctional rhizobiome performs several metabolic functions including carbon fixation, nitrogen, phosphorus, sulfur, iron and aromatic compound metabolism, stress response, secondary metabolite synthesis and virulence, disease, and defense. Abundance of genes linked with N, P, S, Fe and aromatic compound metabolism and phytohormone synthesis—along with other prominent functions—clearly justifies growth, development, and survival of the plants under nutrient deprived dry environment conditions. The dominance of actinobacteria, the known antibiotic producing communities shows that the kodo rhizobiome possesses metabolic capabilities to defend themselves against biotic stresses. The study opens avenues to revisit multi-functionalities of the crop rhizosphere for establishing link between taxonomic abundance and targeted functions that help plant growth and development in stressed and nutrient deprived soil conditions. It further helps in understanding the role of rhizosphere microbiome in adaptation and survival of plants in harsh abiotic conditions.

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“…The human microbiota consists of trillions of symbiotic microbial cells that not only help its host to digest dietary components(1-3), metabolize drugs(4-6), and regulate immune system(7-9) but also produce complex small molecules such as antimicrobial nonribosomal peptides (NRPs) and polyketides (PKs)(10-12). Recent computational mining efforts of genomes and metagenomes of the human microbiome revealed a vast diversity (∼14,000) of putative biosynthetic gene clusters (BGCs) encoding small molecules across all human body sites(13), of which many represented NRP, PK and hybrid NRP-PK small molecules.…”

Section: Figurementioning

confidence: 99%

CariogenicStreptococcus mutansproduces strain-specific antibiotics that impair commensal colonization

Tang

Kudo

Baker

et al. 2019

Preprint

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Streptococcus mutans is a common constituent of dental plaque and an etiologic agent of dental caries (tooth decay). Here we elucidate a biosynthetic pathway, encoded by globally distributed strains of S. mutans, which produces a series of bioactive small molecules including reutericyclin and two N-acyl tetramic acid analogues active against oral commensal bacteria. This pathway may provide S. mutans with a competitive advantage, promoting dysbiosis and caries pathogenesis.

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Natural product discovery from the human microbiome

Cited by 69 publications

References 72 publications

A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli

A multiproducer microbiome generates chemical diversity in the marine sponge Mycale hentscheli

Rhizosphere Metagenomics of Paspalum scrobiculatum L. (Kodo Millet) Reveals Rhizobiome Multifunctionalities

CariogenicStreptococcus mutansproduces strain-specific antibiotics that impair commensal colonization

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