Format

Send to

Choose Destination
ACS Synth Biol. 2013 Jul 19;2(7):379-83. doi: 10.1021/sb3001062. Epub 2012 Nov 5.

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

Author information

1
Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093-0204, United States.

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.

PMID:
23654255
PMCID:
PMC3716868
DOI:
10.1021/sb3001062
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center