Enzymatic formation of a resorcylic acid by creating a structure-guided single-point mutation in stilbene synthase

Namita Bhan, Lingyun Li, Chao Cai, Peng Xu, Robert J. Linhardt*, Mattheos A.G. Koffas

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

A novel C17 resorcylic acid was synthesized by a structure-guided Vitis vinifera stilbene synthase (STS) mutant, in which threonine 197 was replaced with glycine (T197G). Altering the architecture of the coumaroyl binding and cyclization pocket of the enzyme led to the attachment of an extra acetyl unit, derived from malonyl-CoA, to p-coumaroyl-CoA. The resulting novel pentaketide can be produced strictly by STS-like enzymes and not by Chalcone synthase-like type III polyketide synthases; due to the unique thioesterase like activity of STS-like enzymes. We utilized a liquid chromatography mass spectrometry-based data analysis approach to directly compare the reaction products of the mutant and wild type STS. The findings suggest an easy to employ platform for precursor-directed biosynthesis and identification of unnatural polyketides by structure-guided mutation of STS-like enzymes.

Original languageEnglish
Pages (from-to)167-173
Number of pages7
JournalProtein Science
Volume24
Issue number2
DOIs
StatePublished - 1 Feb 2015
Externally publishedYes

Keywords

  • novel non-natural polyphenols
  • resorcylic acid
  • stilbene synthase
  • structure-guided mutants
  • type III polyketides synthases

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