Mechanism of the Oxidative Ring-Closure Reaction during Gliotoxin Biosynthesis by Cytochrome P450 GliF.

ABSTRACT: During gliotoxin biosynthesis in fungi, the cytochrome P450 GliF enzyme catalyzes an unusual C-N ring-closure step while also an aromatic ring is hydroxylated in the same reaction cycle, which may have relevance to drug synthesis reactions in biotechnology. However, as the details of the reaction mechanism are still controversial, no applications have been developed yet. To resolve the mechanism of gliotoxin biosynthesis and gain insight into the steps leading to ring-closure, we ran a combination of molecular dynamics and density functional theory calculations on the structure and reactivity of P450 GliF and tested a range of possible reaction mechanisms, pathways and models. The calculations show that, rather than hydrogen atom transfer from the substrate to Compound I, an initial proton

SUBMITTER: Qureshi M 

PROVIDER: S-EPMC11354885 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature