Diaryl Ether Formation by a Versatile Thioesterase Domain

J Am Chem Soc. 2022 Jun 8;144(22):9554-9558. doi: 10.1021/jacs.2c02813. Epub 2022 May 31.

Abstract

Oxidative coupling and oxidative rearrangement are two of the most common biosynthetic strategies to form diaryl ethers. In contrast, enzymatic diaryl ether generation that proceeds in a nonoxidative manner has not been characterized thus far. Here, we discovered a versatile thioesterase (TE) domain from the nonreducing polyketide synthase (nrPKS) AN7909, which catalyzes diaryl ether formation through a series of successive steps involving esterification, a Smiles rearrangement, and hydrolysis. Further mutations and biochemical analyses with synthetic mimic substrates provide insight into the proposed catalytic process of the TE domain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ether*
  • Polyketide Synthases* / chemistry
  • Polyketide Synthases* / genetics
  • Thiolester Hydrolases / chemistry

Substances

  • Ether
  • Polyketide Synthases
  • Thiolester Hydrolases