Oxidative Dearomatization of PLP in Thiamin Pyrimidine Biosynthesis in Candida albicans

J Am Chem Soc. 2023 Mar 1;145(8):4421-4430. doi: 10.1021/jacs.2c08560. Epub 2023 Feb 20.

Abstract

The yeast thiamin pyrimidine synthase THI5p catalyzes one of the most complex organic rearrangements found in primary metabolism. In this reaction, the active site His66 and PLP are converted to thiamin pyrimidine in the presence of Fe(II) and oxygen. The enzyme is a single-turnover enzyme. Here, we report the identification of an oxidatively dearomatized PLP intermediate. We utilize oxygen labeling studies, chemical-rescue-based partial reconstitution experiments, and chemical model studies to support this identification. In addition, we also identify and characterize three shunt products derived from the oxidatively dearomatized PLP.

Publication types

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

MeSH terms

  • Candida albicans*
  • Oxidative Stress
  • Oxygen
  • Pyrimidines* / chemistry
  • Thiamine / chemistry

Substances

  • Pyrimidines
  • Thiamine
  • Oxygen