Abstract

Many microorganisms produce natural products that form the basis of antimicrobials, antivirals, and other drugs. Genome mining is routinely used to complement screening-based workflows to discover novel natural products. Since 2011, the "antibiotics and secondary metabolite analysis shell—antiSMASH" (https://antismash.secondarymetabolites.org/) has supported researchers in their microbial genome mining tasks, both as a free-to-use web server and as a standalone tool under an OSI-approved open-source license. It is currently the most widely used tool for detecting and characterising biosynthetic gene clusters (BGCs) in bacteria and fungi. Here, we present the updated version 6 of antiSMASH. antiSMASH 6 increases the number of supported cluster types from 58 to 71, displays the modular structure of multi-modular BGCs, adds a new BGC comparison algorithm, allows for the integration of results from other prediction tools, and more effectively detects tailoring enzymes in RiPP clusters.

Highlights

  • Natural compounds produced by microorganisms form the basis of many drugs [1]

  • As the ClusterBlast algorithm is based on protein sequence comparisons by local alignments (initially using BLAST [31], using DIAMOND [32]), it does not perform optimally on multimodular enzymes like NRPSes and PKSes

  • Biosynthetic components are the collection of gene products matching one of antiSMASH’s biosynthetic gene clusters (BGCs) detection profiles, gene products with a functional annotation due to either their presence in an antiSMASH detection rule or based on the classification of their secondary metabolite clusters of orthologous groups class, and, if applicable, NRPS and polyketide synthases (PKSs) domains

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Summary

Introduction

Natural compounds produced by microorganisms form the basis of many drugs [1]. Traditionally, new compounds were discovered by extracting, chemically isolating, purifying, and testing from natural sources. Since its initial release in 2011, antiSMASH [11,12,13,14,15] has become the most widely used tool for mining microbial genomes for secondary/specialised metabolite (SM) biosynthetic gene clusters (BGCs) and is regarded as the gold standard.

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