The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
A roadmap for natural product discovery based on large-scale genomics and metabolomics
Open accessAbstract
Actinobacteria encode a wealth of natural product biosynthetic gene clusters (NPGCs), whose systematic study is complicated by numerous repetitive motifs. By combining several metrics we developed a method for global classification of these gene clusters into families (GCFs) and analyzed the biosynthetic capacity of Actinobacteria in 830 genome sequences, including 344 obtained for this project. The GCF network, comprised of 11,422 gene clusters grouped into 4,122 GCFs, was validated in hundreds of strains by correlating confident mass spectrometric detection of known small molecules with the presence/absence of their established biosynthetic gene clusters. The method also linked previously unassigned GCFs to known natural products, an approach that will enable de novo, bioassay-free discovery of novel natural products using large data sets. Extrapolation from the 830-genome dataset reveals that Actinobacteria encode hundreds of thousands of future drug leads, while the strong correlation between phylogeny and GCFs frames a roadmap to efficiently access them.
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Versatile and open software for comparing large genomes
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De novo assembly of human genomes with massively parallel short read sequencing
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Cited by
Minimum Information about a Biosynthetic Gene cluster
Medema, M. H., Kottmann, R., Yilmaz, P., Cummings, M., Biggins, J. B., Blin, K., de Bruijn, I., Chooi, Y. H., Claesen, J., Coates, R. C., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1890 · Cited by 873
The evolution of genome mining in microbes – a review
Ziemert, N., Alanjary, M., & Weber, T. (2016) · Natural Product Reports · doi:10.1039/c6np00025h · Cited by 688
Actinomycetes: Still a source of novel antibiotics
Genilloud, O. (2017) · Natural Product Reports · doi:10.1039/c7np00026j · Cited by 465
Liu, X., & Locasale, J. W. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.01.004 · Cited by 453
Ecology and genomics of Actinobacteria: new concepts for natural product discovery
van Bergeijk, D. A., Terlouw, B. R., Medema, M. H., & van Wezel, G. P. (2020) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0379-y · Cited by 448
Metadata
- Authors
- Doroghazi, J. R., Albright, J. C., Goering, A. W., Ju, K.-S., Haines, R. R., Tchalukov, K. A., Labeda, D. P., Kelleher, N. L., & Metcalf, W. W.
- Venue
- Nature Chemical Biology
- Published
- 2014-09-28
- Volume
- 10
- Issue
- 11
- Pages
- 963-968
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2041537722
- Cited by
- 476
- References
- 6
- FWCI
- 31.82
- Type
- journal article
- Language
- en
- Open access
- green
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- Doroghazi, J. R., Albright, J. C., Goering, A. W., Ju, K.-S., Haines, R. R., Tchalukov, K. A., Labeda, D. P., Kelleher, N. L., & Metcalf, W. W. (2014). A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nature Chemical Biology. https://doi.org/10.1038/nchembio.1659
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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