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

Abstract

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

Gut Symbionts from Distinct Hosts Exhibit Genotoxic Activity via Divergent Colibactin Biosynthesis Pathways

“…Little is known about natural products involved in symbioses with eukaryotic hosts (14,(22)(23)(24). In particular, their roles and distributions among gut communities have mainly remained elusive.…”

“…In particular, their roles and distributions among gut communities have mainly remained elusive. Furthermore, natural products of animal-dwelling symbionts often reveal chemical and structural properties distinct from those of free-living microbes and thus hold promise for novel drug discovery (24,25). In Escherichia coli strains and related coliform Enterobacteriaceae, a hybrid NRPS-PKS biosynthetic gene cluster was found to be involved in symbiotic interactions in the human gut (26)(27)(28)(29).…”

The Influence of Brazilian Biodiversity on Searching for Human Use Pharmaceuticals

“…Finally there was a recent very intriguing report showing the presence of pederin-like compound, nosperin (19) in a lichen, so the genes are extremely widespread. 45 As mentioned earlier, pederin certainly excited synthetic organic chemists and over the years, effectively all of the molecules that contain the pederin backbone, even when ring-opened as in irciniastatin (20) Thus what started as a discussion of the toxin produced by the blister beetle that was known in Brazilian forests/ jungles, led to the ability to identify and express genetic loci related to the biosynthesis of the agent, but then moved into areas not even thought to be possible; that the beetle toxin was in fact, used by "Mother Nature" (or biodiversity) to generate molecules in organisms as diverse as shallow and deep water marine sponges, warm and cold waters environments and even terrestrial lichens. None of these were even thought of in the wildest dreams of the original scientists working on beetle toxins irrespective of their geographic locations.…”

Publication impact in sponge chemical and microbial ecology

“…Today's major themes in sponge chemical ecology are to test the bioactivity of natural products regardless of the origin of these metabolites (Wright et al 2011, Freeman and Gleason 2012, Nuñez-Pons et al 2012 and to screen for new drugs with potential pharmacological and biotechnological applications (Leal et al 2012a,b, Acevedo et al 2013, Kampa et al 2013). There are several papers about the variability of bioactive compounds at multiple temporal and spatial scales (Sacristán-Soriano et al 2011a, 2012, Evans-Illidge et al 2013) and many others that link host metabolites with symbionts from the sponge (Hochmuth et al 2010, Penesyan et al 2010, Indraningrat et al 2016.…”

“…The vast majority of studies in chemical ecology deal with the biological activity of natural products from sponges (Wright et al 2011, Freeman and Gleason 2012, Nuñez-Pons et al 2012 and their biotechnological potential (Leal et al 2012a, b, Acevedo et al 2013, Kampa et al 2013). However, sponges harbour complex microbial communities that must be taken into consideration in the ecology research field.…”