Enzymatic Metal-Hydrogen Atom Transfer with a Cobalt Protoporphyrin Cofactor.

ABSTRACT: Introduction of unnatural cofactors in biocatalysis may open the door to new reactive enzymatic intermediates, and in turn, new biochemical reactions. Here, we employed a de novo biosynthesized, non-natural cofactor, cobalt protoporphyrin IX (CoPPIX), to generate a mononuclear cobalt hydride in the active site of CYP119, a model P450 enzyme. We show that this cobalt hydride intermediate engages in metal-hydrogen atom transfer (MHAT) reactivity, a well-studied and highly utilized reactivity pattern in synthetic chemistry, but which is not known to operate in Nature. We paired convenient in vivo CoPPIX biosynthesis with a colorimetric screen to enable rapid directed evolution. Thus, we engineered CYP119 for MHAT-mediated deallylation of nitrophenols, with the goal of generating not one proli

SUBMITTER: Masonheimer CL 

PROVIDER: S-EPMC12903868 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature