IMG-ABC: new features for bacterial secondary metabolism analysis and targeted biosynthetic gene cluster discovery in thousands of microbial genomes

Abstract

Secondary metabolites produced by microbes have diverse biological functions, which makes them a great potential source of biotechnologically relevant compounds with antimicrobial, anti-cancer and other activities. The proteins needed to synthesize these natural products are often encoded by clusters of co-located genes called biosynthetic gene clusters (BCs). In order to advance the exploration of microbial secondary metabolism, we developed the largest publically available database of experimentally verified and predicted BCs, the Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters (IMG-ABC) (https://img.jgi.doe.gov/abc/). Here, we describe an update of IMG-ABC, which includes ClusterScout, a tool for targeted identification of custom biosynthetic gene clusters across 40 000 isolate microbial genomes, and a new search capability to query more than 700 000 BCs from isolate genomes for clusters with similar Pfam composition. Additional features enable fast exploration and analysis of BCs through two new interactive visualization features, a BC function heatmap and a BC similarity network graph. These new tools and features add to the value of IMG-ABC's vast body of BC data, facilitating their in-depth analysis and accelerating secondary metabolite discovery.

Environmental and Intestinal Phylum Firmicutes Bacteria Metabolize the Plant Sugar Sulfoquinovose via a 6-Deoxy-6-sulfofructose Transaldolase Pathway

“…We searched for bacterial genomes that harbor sft -gene clusters using IMG's ( https://img.jgi.doe.gov ) Ortholog Neighborhood Viewer and Cluster Scout ( Hadjithomas et al., 2017 ) and retrieved a total of 189 candidate clusters, predominantly in members of the classes Bacilli and Clostridia (phylum Firmicutes), e.g., in members of the genera Bacillus , Enterococcus , Lactobacillus , Butyrivibrio , Pseudobutyrivibrio , Eubacterium , and Clostridium , and also in individual genomes of members of the phyla Fusobacteria, Chloroflexi, Actinobacteria, Spirochaetes, and Thermotogae. Representative gene-cluster architectures comprising the key genes for enzymes SftITD as well as for SQ-glyceride cleavage of the sulfolipid (SftG, alpha -glucosidases), and predicted genes for transport systems (import of SQ and excretion of SL or DHPS), regulation and metabolism of glycerol, if present (Discussion), are illustrated in Figure 5 .…”

Increased diversity of peptidic natural products revealed by modification-tolerant database search of mass spectra

“…Each identified PNP was found in 9.7 various PNP forms on average with the maximum value equal to 239 for tolybyssidin A. Our analysis adds a “chemical” dimension to the recently revealed PNP diversity at the biosynthetic gene cluster (BGC) level 33, 34 . We further revealed that related bacteria are likely to produce similar PNP variants rather than identical PNPs (see the Methods section).…”

Genome Mining as New Challenge in Natural Products Discovery

“…(iii) "Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters" (IMG/ABC) [21], launched in 2015, is a large open web database of known predicted microbial BGCs able to associate BGCs with secondary metabolites (SMs) and analyze both BGCs and SMs. In this way, it offers the ability of finding similar function between BGCs present in database and BGCs to be identified [22].…”