Superoxide-mediated O₂ activation drives radical cyclization in ergot alkaloid biosynthesis

Abstract

Conventional heme enzymes utilize iron-oxygen intermediates to activate substrates and drive reactions. Recently, Chen et al. discovered a novel NADPH-independent superoxide mechanism of heme catalase EasC, which facilitates an O₂-dependent radical oxidative cyclization reaction during ergot alkaloid biosynthesis. This enzyme coordinates superoxide-mediated catalysis by connecting spatially distinct NADPH-binding pocket and heme pocket via a slender tunnel, offering a novel perspective on the catalytic mechanisms of heme enzymes in nature.

Keywords

Ergot alkaloids / Heme catalase / Superoxide / Cooperative catalysis / Radical oxidative cyclization

Declaration of Competing Interest

Given his role as Executive Editor, Dr. Shengying Li had no involvement in the peer review of this article, and had no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Dr. Jiazhang Lian.

CRediT Authorship Contribution Statement

Yuanyuan Jiang: Writing - review & editing, Writing - original draft. Zhong Li: Writing - review & editing, Writing - original draft. Shengying Li: Writing - review & editing, Writing - original draft.

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (32025001, 32300021, 32200017).

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