antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences

TLDR

Bacterial and fungal secondary metabolism produces diverse bioactive compounds, but identifying all gene clusters in newly sequenced genomes is difficult because of biochemical heterogeneity, unknown enzymes, and fragmented bioinformatics resources. The authors aim to provide antiSMASH, a comprehensive pipeline that identifies biosynthetic loci for all known secondary metabolite classes in microbial genomes. antiSMASH aligns detected gene clusters to a comprehensive database of known clusters and integrates existing secondary‑metabolite analysis tools into a single interactive interface. antiSMASH is publicly available at http://antismash.secondarymetabolites.org.

Abstract

Bacterial and fungal secondary metabolism is a rich source of novel bioactive compounds with potential pharmaceutical applications as antibiotics, anti-tumor drugs or cholesterol-lowering drugs. To find new drug candidates, microbiologists are increasingly relying on sequencing genomes of a wide variety of microbes. However, rapidly and reliably pinpointing all the potential gene clusters for secondary metabolites in dozens of newly sequenced genomes has been extremely challenging, due to their biochemical heterogeneity, the presence of unknown enzymes and the dispersed nature of the necessary specialized bioinformatics tools and resources. Here, we present antiSMASH (antibiotics & Secondary Metabolite Analysis Shell), the first comprehensive pipeline capable of identifying biosynthetic loci covering the whole range of known secondary metabolite compound classes (polyketides, non-ribosomal peptides, terpenes, aminoglycosides, aminocoumarins, indolocarbazoles, lantibiotics, bacteriocins, nucleosides, beta-lactams, butyrolactones, siderophores, melanins and others). It aligns the identified regions at the gene cluster level to their nearest relatives from a database containing all other known gene clusters, and integrates or cross-links all previously available secondary-metabolite specific gene analysis methods in one interactive view. antiSMASH is available at http://antismash.secondarymetabolites.org .