Research Highlights
- Subject Category:
Published online: 9 July 2008 | doi:10.1038/nchina.2008.157
Antibiotic synthesis: Last but not least
Jasmine Farsarakis
Abstract
Insights into the late-stage modifications of nanchangmycin shed light on the biosynthetic pathways of other similar antibiotics
Original article citation
Mechanism of thioesterase-catalyzed chain release in the biosynthesis of the polyether antibiotic nanchangmycin. Chem. Biol. 15, 449–458 (2008).Introduction
© (2008) Elsevier
Nanchangmycin, a polyether antibiotic produced by the soil bacteria Streptomyces nanchangensis, is used as a growth promotant in poultry farming. Zixin Deng at Shanghai Jiao Tong University, David Cane at Brown University, and co-workers1 have identified the last two steps in the biosynthesis of nanchangmycin. The finding will give considerable insights into how other polyether antibiotics, which are widely used in meat production, are synthesized.
It has been known that the polyketide backbone of polyether — the first step in the biosynthesis — is assembled by a special class of enzymes called polyketide synthases. A variety of late-stage modifications, including the attachment of methyl and hydroxyl groups, yield the final structure of the polyether.
In the case of nanchangmycin, the penultimate step involves the substitution of a glycol group for a C-19 hydroxyl group (see image), which is handled by the enzyme glycosyl transferase. The researchers found that without the glycosyl transferase gene nanG5, S. nanchangensis could only produce nanchangmycin that lacks deoxy sugar.
Further investigation showed that the enzyme thioesterase NanE catalyses the last step in the biosynthesis — the release of the hydroxyl group. Components of NanE, namely the amino acids Ser96, His261 and Asp120, were shown to be essential for this last step.
The authors of this work are from:
Laboratory of Microbial Metabolism and School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, China; Department of Chemistry, Brown University, Providence, Rhode Island, USA.
Reference
- Liu, T., Lin, X., Zhou, X., Deng, Z. & Cane, D. E. Mechanism of thioesterase-catalyzed chain release in the biosynthesis of the polyether antibiotic nanchangmycin. Chem. Biol. 15, 449–458 (2008). | Article | PubMed | ChemPort |
