Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species

Abstract

BackgroundGenome mining tools have enabled us to predict biosynthetic gene clusters that might encode compounds with valuable functions for industrial and medical applications. With the continuously increasing number of genomes sequenced, we are confronted with an overwhelming number of predicted clusters. In order to guide the effective prioritization of biosynthetic gene clusters towards finding the most promising compounds, knowledge about diversity, phylogenetic relationships and distribution patterns of biosynthetic gene clusters is necessary.ResultsHere, we provide a comprehensive analysis of the model actinobacterial genus Amycolatopsis and its potential for the production of secondary metabolites. A phylogenetic characterization, together with a pan-genome analysis showed that within this highly diverse genus, four major lineages could be distinguished which differed in their potential to produce secondary metabolites. Furthermore, we were able to distinguish gene cluster families whose distribution correlated with phylogeny, indicating that vertical gene transfer plays a major role in the evolution of secondary metabolite gene clusters. Still, the vast majority of the diverse biosynthetic gene clusters were derived from clusters unique to the genus, and also unique in comparison to a database of known compounds. Our study on the locations of biosynthetic gene clusters in the genomes of Amycolatopsis’ strains showed that clusters acquired by horizontal gene transfer tend to be incorporated into non-conserved regions of the genome thereby allowing us to distinguish core and hypervariable regions in Amycolatopsis genomes.ConclusionsUsing a comparative genomics approach, it was possible to determine the potential of the genus Amycolatopsis to produce a huge diversity of secondary metabolites. Furthermore, the analysis demonstrates that horizontal and vertical gene transfer play an important role in the acquisition and maintenance of valuable secondary metabolites. Our results cast light on the interconnections between secondary metabolite gene clusters and provide a way to prioritize biosynthetic pathways in the search and discovery of novel compounds.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4809-4) contains supplementary material, which is available to authorized users.

Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria

“…We showed that BGCs and CGCs in Streptomyces are highly diverse and exhibit variable patterns of phylogenetic distribution, with hybrid BGCs and inter-strain variation further expanding the BGC repertoire present in any one genome. These findings are consistent with recent reports in other genera of Actinobacteria 6,18,19 and also highlight the power of mining the genomes of closely related strains. In a recent study of ten Streptomyces strains with 16S rRNA gene sequences that are all identical to the type strain of Streptomyces cyaneofuscatus and hence are considered the same species, no two strains appear to exhibit identical secondary metabolomic profiles 32 .…”

“…We characterized the biosynthetic diversity in 1,110 Streptomyces genomes using antiSMASH 17 (Supplementary Table S1). We detected a total of 34 major classes of BGCs, which is consistent with previous reports in other Actinobacteria genera such as Salinispora and Amycolatopsis 6,18,19 . , Streptomyces thermoautotrophicus H1 (n = 9 BGCs) and S. thermoautotrophicus UBT1 (n = 11 BGCs).…”

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“…Recent comparative genomics of the genus Amycolatopsis, a large, widely distributed genus well-known as a source of bioactive metabolites, illustrates the power of this strategy. The pan-genome of members of this genus comprises a small core genome largely involved with translation and ribosome biogenesis and a 'huge' accessory genome that includes numerous genes encoding biosynthesis of specialized metabolites [55]. Phylogenetic analysis of the genus revealed four distinct lineages that correlated perfectly in their capacities to produce specialized metabolites; moreover, the extensive diversity of BGCs revealed that the majority were unique to Amycolatopsis.…”

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