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Designed biosynthesis of 36-methyl-FK506 by polyketide precursor pathway engineering

Title
Designed biosynthesis of 36-methyl-FK506 by polyketide precursor pathway engineering
Authors
Lechner A.Wilson M.C.Ban Y.H.Hwang J.-Y.Yoon Y.J.Moore B.S.
Ewha Authors
윤여준
SCOPUS Author ID
윤여준scopus
Issue Date
2013
Journal Title
ACS Synthetic Biology
ISSN
2161-5063JCR Link
Citation
vol. 2, no. 7, pp. 379 - 383
Indexed
SCIE; SCOPUS WOS scopus
Abstract
The polyketide synthase (PKS) biosynthetic code has recently expanded to include a newly recognized group of extender unit substrates derived from α,β-unsaturated acyl-CoA molecules that deliver diverse side chain chemistry to polyketide backbones. Herein we report the identification of a three-gene operon responsible for the biosynthesis of the PKS building block isobutyrylmalonyl-CoA associated with the macrolide ansalactam A from the marine bacterium Streptomyces sp. CNH189. Using a synthetic biology approach, we engineered the production of unnatural 36-methyl-FK506 in Streptomyces sp. KCTC 11604BP by incorporating the branched extender unit into FK506 biosynthesis in place of its natural C-21 allyl side chain, which has been shown to be critical for FK506's potent immunosuppressant and neurite outgrowth activities. © 2012 American Chemical Society.
DOI
10.1021/sb3001062
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자연과학대학 > 화학·나노과학전공 > Journal papers
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