IMG-ABC: A Knowledge Base To Fuel Discovery of Biosynthetic Gene Clusters and Novel Secondary Metabolites

Hadjithomas, Michalis; Chen, I-Min Amy; Chu, Ken; Ratner, Anna; Palaniappan, Krishna; Szeto, Ernest; Huang, Jinghua; Reddy, T. B. K.; Cimermančič, Peter; Fischbach, Michael A.; Ivanova, Natalia; Markowitz, Victor; Kyrpides, Nikos C.; Pati, Amrita

doi:10.1128/mbio.00932-15

Cited by 97 publications

(92 citation statements)

References 38 publications

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“…Most of the predicted BC products were unclassified, reflecting both the limited information available for characterized natural products and the rich genomic resource of biosynthetic capabilities contributed by GEBA-I. For example, nine new phenazine pathways with novel operon structures and genes were identified in the GEBA-I genomes 23 . Phenazines are a large class of nitrogencontaining heterocyclic secondary metabolites that have potent antimicrobial and antifungal activity, and are produced by a wide (c) Maximum 16S rRNA distance of genomes contributing a GEBA-I-only protein cluster.…”

Section: Biosynthetic Clusters For Secondary Metabolitesmentioning

confidence: 99%

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1,003 reference genomes of bacterial and archaeal isolates expand coverage of the tree of life

et al. 2017

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We present 1,003 reference genomes that were sequenced as part of the Genomic Encyclopedia of Bacteria and Archaea (GEBA) initiative, selected to maximize sequence coverage of phylogenetic space. These genomes double the number of existing type strains and expand their overall phylogenetic diversity by 25%. Comparative analyses with previously available finished and draft genomes reveal a 10.5% increase in novel protein families as a function of phylogenetic diversity. The GEBA genomes recruit 25 million previously unassigned metagenomic proteins from 4,650 samples, improving their phylogenetic and functional interpretation. We identify numerous biosynthetic clusters and experimentally validate a divergent phenazine cluster with potential new chemical structure and antimicrobial activity. This Resource is the largest single release of reference genomes to date. Bacterial and archaeal isolate sequence space is still far from saturated, and future endeavors in this direction will continue to be a valuable resource for scientific discovery.

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Section: Biosynthetic Clusters For Secondary Metabolitesmentioning

confidence: 99%

“…A total of 23,839 BCs were predicted from 1,003 GEBA-I genomes using the IMG-ABC system 23 . Three Pseudonocardiaceae genomes (Pseudonocardia acaciae, P. spinosispora and Sciscionella marina) encoded the greatest total number of BCs among all GEBA-I genomes (Fig.…”

Section: Biosynthetic Clusters For Secondary Metabolitesmentioning

confidence: 99%

1,003 reference genomes of bacterial and archaeal isolates expand coverage of the tree of life

et al. 2017

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“…In order to determine which RMA gene clusters are similar to already sequenced, but not necessarily experimentally confirmed, gene clusters, we used a gene cluster similarity networking approach with the JGI Atlas of Biosynthetic gene Clusters (ABC) database as our comparison set (Hadjithomas et al, 2015). This dataset is composed of all genomes deposited in JGI and run with ClusterFinder and antiSMASH to locate and annotate secondary metabolite gene clusters.…”

Section: Gene Cluster Similarity Networkmentioning

confidence: 99%

Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters

et al. 2016

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Traditional natural product discovery methods have nearly exhausted the accessible diversity of microbial chemicals, making new sources and techniques paramount in the search for new molecules. Marine actinomycete bacteria have recently come into the spotlight as fruitful producers of structurally diverse secondary metabolites, and remain relatively untapped. In this study, we sequenced 21 marine-derived actinomycete strains, rarely studied for their secondary metabolite potential and under-represented in current genomic databases. We found that genome size and phylogeny were good predictors of biosynthetic gene cluster diversity, with larger genomes rivalling the well-known marine producers in the Streptomyces and Salinispora genera. Genomes in the Micrococcineae suborder, however, had consistently the lowest number of biosynthetic gene clusters. By networking individual gene clusters into gene cluster families, we were able to computationally estimate the degree of novelty each genus contributed to the current sequence databases. Based on the similarity measures between all actinobacteria in the Joint Genome Institute's Atlas of Biosynthetic gene Clusters database, rare marine genera show a high degree of novelty and diversity, with Corynebacterium, Gordonia, Nocardiopsis, Saccharomonospora and Pseudonocardia genera representing the highest gene cluster diversity. This research validates that rare marine actinomycetes are important candidates for

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“…Fortunately, advances in high-quality genome sequences of Streptomyces isolates ( Figure 1) and other secondary metabolite-producing organisms have sparked the development of such specialized computational resources, including databases and genome/compound mining tools, and the representative ones are presented herein. First, BGC databases allow for easy access and evaluation of curated and predicted BGCs, such as the Minimum Information on Biosynthetic Gene Clusters (MIBiG), [20] the Integrated Microbial Genomes Atlas of Biosynthetic gene Clusters (IMG-ABC), [21] and the antiSMASH database. [22] For the secondary metabolite compounds, several comprehensive databases exist as well, including NORINE [23] specifically for non-ribosomal peptides (NRPs), Antibiotic'ome [24] for the predicted molecular targets of antibiotics, and StreptomeDB, [25] which presents information on compounds produced by streptomycetes.…”

Section: Characterization Of Bgcs and Their Secondary Metabolites Thrmentioning

confidence: 99%

Toward Systems Metabolic Engineering of Streptomycetes for Secondary Metabolites Production

Robertsen

Weber

Kim

et al. 2017

Biotechnology Journal

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Streptomycetes are known for their inherent ability to produce pharmaceutically relevant secondary metabolites. Discovery of medically useful, yet novel compounds has become a great challenge due to frequent rediscovery of known compounds and a consequent decline in the number of relevant clinical trials in the last decades. A paradigm shift took place when the first whole genome sequences of streptomycetes became available, from which silent or "cryptic" biosynthetic gene clusters (BGCs) were discovered. Cryptic BGCs reveal a so far untapped potential of the microorganisms for the production of novel compounds, which has spurred new efforts in understanding the complex regulation between primary and secondary metabolism. This new trend has been accompanied with development of new computational resources (genome and compound mining tools), generation of various high-quality omics data, establishment of molecular tools, and other strain engineering strategies. They all come together to enable systems metabolic engineering of streptomycetes, allowing more systematic and efficient strain development. In this review, the authors present recent progresses within systems metabolic engineering of streptomycetes for uncovering their hidden potential to produce novel compounds and for the improved production of secondary metabolites.

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IMG-ABC: A Knowledge Base To Fuel Discovery of Biosynthetic Gene Clusters and Novel Secondary Metabolites

Cited by 97 publications

References 38 publications

1,003 reference genomes of bacterial and archaeal isolates expand coverage of the tree of life

1,003 reference genomes of bacterial and archaeal isolates expand coverage of the tree of life

Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters

Toward Systems Metabolic Engineering of Streptomycetes for Secondary Metabolites Production

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