Aminofutalosine Synthase: Evidence for Captodative and Aryl Radical Intermediates Using β-Scission and SRN1 Trapping Reactions

J Am Chem Soc. 2017 Aug 16;139(32):10952-10955. doi: 10.1021/jacs.7b04209. Epub 2017 Aug 3.

Abstract

Aminofutalosine synthase (MqnE) is a radical SAM enzyme involved in the menaquinone biosynthetic pathway. In this communication, we propose a novel mechanism for this reaction involving the addition of the adenosyl radical to the substrate double bond to form a captodative radical followed by rearrangement and decarboxylation to form an aryl radical anion which is then oxidized by the [4Fe-4S]+2 cluster. Consistent with this proposal, we describe the trapping of the captodative radical and the aryl radical anion using radical triggered C-Br fragmentation reactions. We also describe the trapping of the captodative radical by replacing the vinylic carboxylic acid with an amide.

Publication types

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

MeSH terms

  • Iron-Sulfur Proteins / chemistry
  • Iron-Sulfur Proteins / metabolism*
  • Oxidation-Reduction
  • Substrate Specificity
  • Thermus thermophilus / chemistry
  • Thermus thermophilus / enzymology*
  • Thermus thermophilus / metabolism
  • Vitamin K 2 / metabolism

Substances

  • Iron-Sulfur Proteins
  • Vitamin K 2