Enzyme-Catalyzed Intramolecular Enantioselective Hydroalkoxylation

J Am Chem Soc. 2017 Mar 15;139(10):3639-3642. doi: 10.1021/jacs.7b01089. Epub 2017 Mar 1.


Hydroalkoxylation is a powerful and efficient method of forming C-O bonds and cyclic ethers in synthetic chemistry. In studying the biosynthesis of the fungal natural product herqueinone, we identified an enzyme that can perform an intramolecular enantioselective hydroalkoxylation reaction. PhnH catalyzes the addition of a phenol to the terminal olefin of a reverse prenyl group to give a dihydrobenzofuran product. The enzyme accelerates the reaction by 3 × 105-fold compared to the uncatalyzed reaction. PhnH belongs to a superfamily of proteins with a domain of unknown function (DUF3237), of which no member has a previously verified function. The discovery of PhnH demonstrates that enzymes can be used to promote the enantioselective hydroalkoxylation reaction and form cyclic ethers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biocatalysis
  • Lyases / metabolism*
  • Molecular Structure
  • Phenalenes / metabolism*
  • Quantum Theory
  • Stereoisomerism


  • Phenalenes
  • Lyases
  • herquienone