Abstract

Computational analysis of biosynthetic gene clusters (BGCs) has revolutionized natural product discovery by enabling the rapid investigation of secondary metabolic potential within microbial genome sequences. Grouping homologous BGCs into Gene Cluster Families (GCFs) facilitates mapping their architectural and taxonomic diversity and provides insights into the novelty of putative BGCs, through dereplication with BGCs of known function. While multiple databases exist for exploring BGCs from publicly available data, no public resources exist that focus on GCF relationships. Here, we present BiG-FAM, a database of 29,955 GCFs capturing the global diversity of 1,225,071 BGCs predicted from 209,206 publicly available microbial genomes and metagenome-assembled genomes (MAGs). The database offers rich functionalities, such as multi-criterion GCF searches, direct links to BGC databases such as antiSMASH-DB, and rapid GCF annotation of user-supplied BGCs from antiSMASH results. BiG-FAM can be accessed online at https://bigfam.bioinformatics.nl.

Highlights

  • Microbial secondary metabolism produces a vast array of natural products (NPs) beneficial to the microbes themselves, but sometimes to humans, for use as, e.g. antibiotics, chemotherapeutics, and crop protecting agents [1,2]

  • With the increasing availability of bacterial and fungal genome sequences, biosynthetic gene clusters (BGCs) identification tools like antiSMASH [3] and PRISM [4] have played a critical role in transforming NP discovery into a genome-based endeavor, as they allow the investigation of bioactive compounds a microorganism may produce even if the pathways are not expressed in the lab or when the genomes originate from uncultivated organisms

  • Being the first resource to offer unprecedented access to the ‘global’ biosynthetic space of microbial BGC families, we expect BiG-FAM to become a relevant resource for NP discovery

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Summary

Introduction

Microbial secondary metabolism produces a vast array of natural products (NPs) beneficial to the microbes themselves, but sometimes to humans, for use as, e.g. antibiotics, chemotherapeutics, and crop protecting agents [1,2]. Computational analysis of biosynthetic gene clusters (BGCs) has revolutionized natural product discovery by enabling the rapid investigation of secondary metabolic potential within microbial genome sequences.

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