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Engineering Broader Specificity into an Antibiotic-Producing Polyketide Synthase
Abstract
The wide-specificity loading module for the avermectin-producing polyketide synthase was grafted onto the first multienzyme component (DEBS1) of the erythromycin-producing polyketide synthase in place of the normal loading module. Expression of this hybrid enzyme in the erythromycin producer Saccharopolyspora erythraea produced several novel antibiotic erythromycins derived from endogenous branched-chain acid starter units typical of natural avermectins. Because the avermectin polyketide synthase is known to accept more than 40 alternative carboxylic acids as starter units, this approach opens the way to facile production of novel analogs of antibiotic macrolides.
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Citations
Cited by
Polyketide biosynthesis: a millennium review
Staunton, J., & Weissman, K. J. (2001) · Natural Product Reports · doi:10.1039/a909079g · Cited by 1,641
Self-citationA chain initiation factor common to both modular and aromatic polyketide synthases
Bisang, C., Long, P. F., Corte´s, J., Westcott, J., Crosby, J., Matharu, A.-L., Cox, R. J., Simpson, T. J., Staunton, J., & Leadlay, P. F. (1999) · Nature · doi:10.1038/46829 · Cited by 278
Self-citationThe commercial production of chemicals using pathway engineering
Chotani, G., Dodge, T., Hsu, A., Kumar, M., LaDuca, R., Trimbur, D., Weyler, W., & Sanford, K. (2000) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(00)00234-x · Cited by 234
Translation and Protein Synthesis: Macrolides
Katz, L., & Ashley, G. W. (2005) · Chemical Reviews · doi:10.1021/cr030107f · Cited by 177
Biosensor Guided Polyketide Synthases Engineering for Optimization of Domain Exchange Boundaries
Englund, E., Schmidt, M., Nava, A. A., Klass, S., Keiser, L., Dan, Q., Katz, L., Yuzawa, S., & Keasling, J. D. (2023) · Nature Communications · doi:10.1038/s41467-023-40464-x · Cited by 22
Metadata
- Authors
- Marsden, A. F. A., Wilkinson, B., Cortés, J., Dunster, N. J., Staunton, J., & Leadlay, P. F.
- Venue
- Science
- Published
- 1998-01-09
- Volume
- 279
- Issue
- 5348
- Pages
- 199-202
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1997029030
- Cited by
- 218
- References
- 0
- FWCI
- 20.43
- Type
- journal article
- Language
- en
- Open access
- closed
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- Marsden, A. F. A., Wilkinson, B., Cortés, J., Dunster, N. J., Staunton, J., & Leadlay, P. F. (1998). Engineering Broader Specificity into an Antibiotic-Producing Polyketide Synthase. Science. https://doi.org/10.1126/science.279.5348.199
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.