AntiSMASH 5.0: updates to the secondary metabolite genome mining pipeline.

Kai Blin,Kat Steinke,Rasmus Villebro,Nadine Ziemert,Tilmann Weber,Simon Shaw,Sang Yup Lee,Marnix H Medema

doi:10.1093/nar/gkz310

Abstract

Secondary metabolites produced by bacteria and fungi are an important source of antimicrobials and other bioactive compounds. In recent years, genome mining has seen broad applications in identifying and characterizing new compounds as well as in metabolic engineering. Since 2011, the ‘antibiotics and secondary metabolite analysis shell—antiSMASH’ (https://antismash.secondarymetabolites.org) has assisted researchers in this, both as a web server and a standalone tool. It has established itself as the most widely used tool for identifying and analysing biosynthetic gene clusters (BGCs) in bacterial and fungal genome sequences. Here, we present an entirely redesigned and extended version 5 of antiSMASH. antiSMASH 5 adds detection rules for clusters encoding the biosynthesis of acyl-amino acids, β-lactones, fungal RiPPs, RaS-RiPPs, polybrominated diphenyl ethers, C-nucleosides, PPY-like ketones and lipolanthines. For type II polyketide synthase-encoding gene clusters, antiSMASH 5 now offers more detailed predictions. The HTML output visualization has been redesigned to improve the navigation and visual representation of annotations. We have again improved the runtime of analysis steps, making it possible to deliver comprehensive annotations for bacterial genomes within a few minutes. A new output file in the standard JavaScript object notation (JSON) format is aimed at downstream tools that process antiSMASH results programmatically.

Highlights

Bacterial and fungal natural products constitute a key source of scaffolds for the development of antimicrobials and other drugs [1], and mediate ecological interactions between organisms in various ways [2].Mining genomic data for the presence of biosynthetic pathways that enable organisms to produce such molecules, which are referred to as secondary or specialized metabolites, have become an essential approach that complements activity- and chemistry-guided isolation and identification approaches [3]
A new output file in the standard JavaScript object notation (JSON) format is aimed at downstream tools that process antiSMASH results programmatically
Several independent tools, such as the mass-spectrometry guided peptide mining tool Pep2Path [15], the ‘Antibiotic Resistance Target Seeker’ ARTS [16], the sgRNA design tool CRISPy-web [17], a reverse-tailoring tool to match finished NRPS/PKS structures to antiSMASH-predicted core structures [18] and the biosynthetic gene clusters (BGCs) clustering and classification platform BiG-SCAPE [19] were developed that directly interact with and interpret results generated by antiSMASH and provide information that is outside the scope of a coreantiSMASH analysis

Summary

Introduction

Bacterial and fungal natural products constitute a key source of scaffolds for the development of antimicrobials and other drugs [1], and mediate ecological interactions between organisms in various ways [2].Mining genomic data for the presence of biosynthetic pathways that enable organisms to produce such molecules, which are referred to as secondary or specialized metabolites, have become an essential approach that complements activity- and chemistry-guided isolation and identification approaches [3]. It has established itself as the most widely used tool for identifying and analysing biosynthetic gene clusters (BGCs) in bacterial and fungal genome sequences.

Results

Conclusion