antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline

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.

Bacterial lipopolysaccharide induces settlement and metamorphosis in a marine larva

“…Genomic mining for secondary metabolite gene clusters is an increasingly important tool for identifying of bioactive molecules (77). The successful employment of these techniques relies upon the completeness and correctness of secondary metabolite gene annotations and databases (77); while such databases are improving daily they remain incomplete (53,78,79). Furthermore the presence of secondary metabolite gene clusters in an organism's genome cannot alone determine the presence of the encoded compound but rather the potential for production of that compound (53,78,79).…”

The identification and deletion of the polyketide synthase‐nonribosomal peptide synthase gene responsible for the production of the phytotoxic triticone A/B in the wheat fungal pathogen Pyrenophora tritici‐repentis

“…The M4 genome (NQIK01000001.1) was mined for biosynthetic gene clusters using antiSMASH v5.0 fungal version (Blin et al, 2019). Under 'analysis options', ClusterFinder and Use ClusterFinder algorithm for biosynthetic gene cluster (BGC) border prediction were selected.…”

Chemical Strategies for Visualizing and Analyzing Endogenous Nonribosomal Peptide Synthetase (NRPS) Megasynthetases

“…Discovery of the nonribosomal code residues (eight amino acids) has facilitated the manipulation of substrate‐binding pockets of the A‐domains. The nonribosomal codes lining the active sites of the A‐domains play a key role in selecting the amino acid substrates during NRP biosynthesis, which enables the prediction of NRP structures from the nonribosomal codes extracted from sequence alignments . Reprogramming of the A‐domain mutates these nonribosomal code residues to alter substrate specificity.…”

“…The nonribosomal codes lining the active sites of the A-domains play ak ey role in selecting the amino acid substrates during NRP biosynthesis, which enables the prediction of NRP structures from the nonribosomal codes extracted from sequence alignments. [32][33][34] Reprogramming of the A-domain mutates these nonribosomal code residues to alter substrate specificity. This approachi sl ess likely to cause disruptions in the native protein-protein interactions within an NRPS module, relative to NRPS subunit,m odule, andd omain exchanges.…”