Cis-Double bond formation by thioesterase and transfer by ketosynthase in FR901464 biosynthesis.

Abstract

Modular polyketide synthases (PKSs) are well known to use ketosynthase (KS)-driven carbon-carbon bond formation, dehydratase-mediated dehydration to form double bonds, and product release by thioesterase (TE), all of which are regarded as the "canonical" roles for most polyketide biosyntheses. FR901464 is biosynthesized by a complex acyltransferase-less PKS system involving a nonterminal TE domain and several mutated KS domains. Here we demonstrate that this TE catalyzes the dehydration of the polyketide intermediate to yield a cis-double bond and a mutated KS transfers the nascent polyketide chain with only a cis-double bond to the downstream acyl carrier protein. These findings not only provide new insights into different enzymatic functions of PKS domains but also suggest an alternative strategy for cis-double bond formation during the polyketide assembly line.

• Authors: Hai-Yan He, Man-Cheng Tang, Feng Zhang, Gong-Li Tang
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 136 Issue 12 Pg. 4488-91 (Mar 26 2014) ISSN: 1520-5126 [Electronic] United States
• PMID: 24617828 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FR 901464
• Pyrans
• Spiro Compounds
• Carbon
• Polyketide Synthases

Topics

• Biocatalysis
• Carbon (chemistry)
• Polyketide Synthases (metabolism)
• Pyrans (chemistry, metabolism)
• Spiro Compounds (chemistry, metabolism)