The gutSMASH web server:automated identification of primary metabolic gene clusters from the gut microbiota.

Victòria Pascal Andreu,Dylan Dodd,Marnix H Medema,Jorge Roel-Touris,Michael A Fischbach

doi:10.1093/nar/gkab353

Victòria Pascal Andreu, Dylan Dodd + Show 3 more

Open Access

https://doi.org/10.1093/nar/gkab353

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Abstract

Anaerobic bacteria from the human microbiome produce a wide array of molecules at high concentrations that can directly or indirectly affect the host. The production of these molecules, mostly derived from their primary metabolism, is frequently encoded in metabolic gene clusters (MGCs). However, despite the importance of microbiome-derived primary metabolites, no tool existed to predict the gene clusters responsible for their production. For this reason, we recently introduced gutSMASH. gutSMASH can predict 41 different known pathways, including MGCs involved in bioenergetics, but also putative ones that are candidates for novel pathway discovery. To make the tool more user-friendly and accessible, we here present the gutSMASH web server, hosted at https://gutsmash.bioinformatics.nl/. The user can either input the GenBank assembly accession or upload a genome file in FASTA or GenBank format. Optionally, the user can enable additional analyses to obtain further insights into the predicted MGCs. An interactive HTML output (viewable online or downloadable for offline use) provides a user-friendly way to browse functional gene annotations and sequence comparisons with reference gene clusters as well as gene clusters predicted in other genomes. Thus, this web server provides the community with a streamlined and user-friendly interface to analyze the metabolic potential of gut microbiomes.

Highlights

Microbiome research has received considerable attention in the last decade, charting the taxonomic and functional diversity found in complex ecosystems and the effects on their host
Given the fact that genes encoding for specialized primary metabolic pathways are often found clustered together and evidence exist that the metabolic potential of such bacteria is far from fully uncovered (13), we recently introduced gutSMASH (9), a tool that identifies known as well as potentially novel metabolic gene clusters (MGCs), based on the antiSMASH version 5.0 framework (14)
GutSMASH detects known and putative gene clusters from prominent human gut pathogens Escherichia albertii belongs to the family Enterobacteriaceae and is an emerging enteropathogen (21)

Summary

Introduction

Microbiome research has received considerable attention in the last decade, charting the taxonomic and functional diversity found in complex ecosystems and the effects on their host. Despite the fact that some of these molecules are produced by low-abundance bacteria, they can reach high concentrations in the gut as well as in blood plasma, sometimes comparable to those of therapeutic drugs (2). This is of great interest because these molecules can profoundly modulate host metabolism, immunity, and homeostasis. An example of such an end product is trimethylamine, derived from carnitine and choline metabolism, which is known to be associated with increased risk of cardiovascular disease (3). Another interesting pathway is ethanolamine utilization, which has been indirectly

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