Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters

Abstract

Traditional natural product discovery methods have nearly exhausted the accessible diversity of microbial chemicals, making new sources and techniques paramount in the search for new molecules. Marine actinomycete bacteria have recently come into the spotlight as fruitful producers of structurally diverse secondary metabolites, and remain relatively untapped. In this study, we sequenced 21 marine-derived actinomycete strains, rarely studied for their secondary metabolite potential and under-represented in current genomic databases. We found that genome size and phylogeny were good predictors of biosynthetic gene cluster diversity, with larger genomes rivalling the well-known marine producers in the Streptomyces and Salinispora genera. Genomes in the Micrococcineae suborder, however, had consistently the lowest number of biosynthetic gene clusters. By networking individual gene clusters into gene cluster families, we were able to computationally estimate the degree of novelty each genus contributed to the current sequence databases. Based on the similarity measures between all actinobacteria in the Joint Genome Institute's Atlas of Biosynthetic gene Clusters database, rare marine genera show a high degree of novelty and diversity, with Corynebacterium, Gordonia, Nocardiopsis, Saccharomonospora and Pseudonocardia genera representing the highest gene cluster diversity. This research validates that rare marine actinomycetes are important candidates for

Function-related replacement of bacterial siderophore pathways

“…Indeed certain genera dedicate up to 10% of their genomes to secondary metabolism ( Nett et al , 2009 ), and the genes that are responsible for production of these metabolites usually reside in biosynthetic gene clusters (BGCs). A variety of computer programs and web tools ( Medema et al , 2011 ; Ziemert et al , 2012 ; Skinnider et al , 2015 ; Weber et al , 2015 ) now allow rapid and straightforward detection of BGCs, with recent surveys of bacterial genomes predicting the existence of large numbers of different gene cluster families ( Cimermancic et al , 2014 ; Schorn et al , 2016 ). However, despite the wealth of knowledge concerning the existence of these BGCs, most have yet to be linked to the small molecules they encode.…”

Screening and identification of novel biologically active natural compounds

“…In the marine area, the Fenical group and collaborators at the Scripps Oceanographic Institution in San Diego have published extensively on the potential of marine microbes, usually free-living but at times associated with invertebrates. The examples given earlier on products from co-culture are one aspect; in addition, papers from long-time collaborators Jensen and Moore, and later Dorrestein, give further insight into the vast areas that still have to be investigated 24 , 25 , 92 – 94 . These investigations, when coupled to the methodologies reported by the Piel group on marine-sourced but as-yet-uncultivated microbes (see earlier section), demonstrate the potential of these sources to uncover novel agents that may result from using the “modernized grind and find” and coupling to the latest phenotypic screening techniques.…”

Natural Product Potential of the Genus Nocardiopsis

“…While bioactive compounds were isolated from strains of both marine and terrestrial environments, marine sediments were the richest source of natural products ( Figure 12 ). Almost 22 sequenced genomes from the genus Nocardiopsis are deposited so far in NCBI from various marine and terrestrial habitats [ 51 , 52 , 53 , 54 ]. The genomic screening and chemical investigation by chromatographic ways is the optimal approach for the prediction and rapid discovery of novel secondary metabolites from microbial strains, such as Nocardiopsis .…”