antiSMASH 4.0-improvements in chemistry prediction and gene cluster boundary identification

Abstract

Many antibiotics, chemotherapeutics, crop protection agents and food preservatives originate from molecules produced by bacteria, fungi or plants. In recent years, genome mining methodologies have been widely adopted to identify and characterize the biosynthetic gene clusters encoding the production of such compounds. Since 2011, the 'antibiotics and secondary metabolite analysis shell-antiSMASH' has assisted researchers in efficiently performing this, both as a web server and a standalone tool. Here, we present the thoroughly updated antiSMASH version 4, which adds several novel features, including prediction of gene cluster boundaries using the ClusterFinder method or the newly integrated CASSIS algorithm, improved substrate specificity prediction for non-ribosomal peptide synthetase adenylation domains based on the new SANDPUMA algorithm, improved predictions for terpene and ribosomally synthesized and post-translationally modified peptides cluster products, reporting of sequence similarity to proteins encoded in experimentally characterized gene clusters on a per-protein basis and a domain-level alignment tool for comparative analysis of trans-AT polyketide synthase assembly line architectures. Additionally, several usability features have been updated and improved. Together, these improvements make antiSMASH up-to-date with the latest developments in natural product research and will further facilitate computational genome mining for the discovery of novel bioactive molecules.

Figure 1.

Gene cluster border prediction by the Cluster Assignment by Islands of Sites (CASSIS) algorithm. The fourth cluster on chromosome 1 of Aspergillus nidulans is shown. The cream-colored bar above the gene arrows spans the genes predicted to be clustered by CASSIS. Further genes in the surrounding are displayed for additional context. Similar functionality is available when using ClusterFinder to predict gene cluster borders.

Figure 2.

Visualization of trans-AT PKS assembly-line alignments. The top 15 most closely related assembly lines are visualized together with the query sequence (which represents the identified BGC currently in view). When clicking on a domain, its location (amino acid coordinates) within the parent protein are displayed and clicking on the gray connecting edges will trigger a display of the sequence identity between homologous domains based on a MAFFT multiple sequence alignment.