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Oxidative Dearomatization of PLP in Thiamin Pyrimidine Biosynthesis in Candida albicans.

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.

SUBMITTER: Mondal A

PROVIDER: S-EPMC10848271 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Oxidative Dearomatization of PLP in Thiamin Pyrimidine Biosynthesis in <i>Candida albicans</i>.

Mondal Anushree A Lai Rung-Yi RY Fedoseyenko Dmytro D Giri Nitai N Begley Tadhg P TP

Journal of the American Chemical Society 20230220 8

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 ...[more]

PMID: 36802573

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