Discovery of Pyranoviolin A and Its Biosynthetic Gene Cluster in Aspergillus violaceofuscus.

Xingxing Wei,Yudai Matsuda,Lin Chen,Jian-Wei Tang

doi:10.3389/fmicb.2020.562063

Abstract

A new polyketide-non-ribosomal peptide hybrid molecule, pyranoviolin A (1), was discovered from the genome-sequenced fungus Aspergillus violaceofuscus CBS 115571 and was characterized to be the first pyranonigrin analog harboring the C-3 methoxy group. Examination of the genome sequence of the fungus identified a putative biosynthetic gene cluster of 1, which was designated as the pyv cluster. The gene deletion experiment of the polyketide synthase (PKS)-non-ribosomal peptide synthetase (NRPS) hybrid gene in the cluster confirmed the involvement of the pyv cluster in the pyranoviolin A biosynthesis. Finally, a plausible biosynthetic route leading to 1 has been proposed based on the bioinformatic analysis. Our study indicates that metabolite analysis of genome-sequenced microorganisms whose metabolites have been largely unexplored facilitates the discovery of new secondary metabolites along with their biosynthetic gene clusters.

Highlights

Filamentous fungi have been rich sources for naturally occurring organic compounds and provided many pharmaceutical drugs, as exemplified by penicillins, cyclosporin, and lovastatin
The rapid linking of secondary metabolites to their biosynthetic gene clusters facilitates biosynthetic engineering of important compounds and mining of other related natural products. To examine this concept, we investigated the metabolites produced by the fungus Aspergillus violaceofuscus CBS 115571 (Vesth et al, 2018), and isolated and characterized one new polyketide-non-ribosomal peptide hybrid molecule named pyranoviolin A (1)
We discovered a new polyketide-non-ribosomal peptide hybrid molecule pyranoviolin A (1) from Aspergillus violaceofuscus CBS 115571 and identified the biosynthetic gene cluster of 1 in the genome of the fungus

Summary

Introduction

Filamentous fungi have been rich sources for naturally occurring organic compounds and provided many pharmaceutical drugs, as exemplified by penicillins, cyclosporin, and lovastatin. As more and more microbial genomes have been sequenced, many researchers have been seeking to obtain novel metabolites by activating silent and unexploited biosynthetic gene clusters. This approach, generally described as “genome mining,” has been widely utilized, leading to the discovery of many new natural products (Brakhage and Schroeckh, 2011; Rutledge and Challis, 2015; Zarins-Tutt et al, 2016; Yan et al, 2020). To activate a specific gene cluster, several different strategies could be used, including the overexpression of the pathway-specific transcriptional factor and heterologous expression of the gene cluster. These strategies do not always work, probably due to the presence of “dead,” rather than “silent,” gene clusters (Montiel et al, 2015)

Methods

Results

Conclusion