The DOI matches its Crossref record.
Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A
Open accessAbstract
Significance: Microbes have the genetic capacity to produce large numbers of specialized compounds, yet produce only a small fraction of these in the laboratory. Here we introduce a genetic platform that allows the efficient production of natural product molecules from uncharacterized gene collections. We used transformation-associated recombination in yeast to directly clone and express an orphan biosynthetic gene cluster for the production of the lipopeptide antibiotic taromycin A. With this direct cloning approach, a single genomic capture and expression vector was designed directly from next-generation sequencing data, which precisely captures genetic loci of interest and readily facilitates genetic manipulations. This study highlights a “plug-and-play” approach to cryptic biosynthetic pathways for the discovery and development of natural product drug candidates.
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Citations
Cited by
Discovery of microbial natural products by activation of silent biosynthetic gene clusters
Rutledge, P. J., & Challis, G. L. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3496 · Cited by 986
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
Self-citationThe 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
Antibiotics and the Gut Microbiota
Modi, S. R., Collins, J. J., & Relman, D. A. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72333 · Cited by 667
Actinomycetes: Still a source of novel antibiotics
Genilloud, O. (2017) · Natural Product Reports · doi:10.1039/c7np00026j · Cited by 465
Metadata
- Authors
- Yamanaka, K., Reynolds, K. A., Kersten, R. D., Ryan, K. S., Gonzalez, D. J., Nizet, V., Dorrestein, P. C., & Moore, B. S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2014-01-21
- Volume
- 111
- Issue
- 5
- Pages
- 1957-1962
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2119933619
- Cited by
- 474
- References
- 0
- FWCI
- 32.47
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yamanaka, K., Reynolds, K. A., Kersten, R. D., Ryan, K. S., Gonzalez, D. J., Nizet, V., Dorrestein, P. C., & Moore, B. S. (2014). Direct cloning and refactoring of a silent lipopeptide biosynthetic gene cluster yields the antibiotic taromycin A. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1319584111
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