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

TitleDesigned biosynthesis of 36-methyl-FK506 by polyketide precursor pathway engineering.
Publication TypeJournal Article
Year of Publication2013
AuthorsLechner A, Wilson MC, Ban YH, Hwang J-Y, Yoon YJ, Moore BS
JournalACS synthetic biology
Volume2
Issue7
Pagination379-83
Date Published2013 Jul 19
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.

DOI10.1111/j.1438-8677.2012.00675.x
Alternate JournalACS Synth Biol