Campus Units

Biochemistry, Biophysics and Molecular Biology, Roy J. Carver Department of

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

5-22-2018

Journal or Book Title

Angewandte Chemie International Edition

Volume

57

Issue

21

First Page

6082

Last Page

6085

DOI

10.1002/anie.201713403

Abstract

Biosynthesis of the gibberellin (GA) plant hormones evolved independently in plants and microbes, but the pathways proceed by similar transformations. The combined demethylation and γ‐lactone ring forming transformation is of significant mechanistic interest, yet remains unclear. The relevant CYP112 from bacteria was probed by activity assays and 18O2‐labeling experiments. Notably, the ability of tert‐butyl hydroperoxide to drive this transformation indicates use of the ferryl‐oxo (Compound I) from the CYP catalytic cycle for this reaction. Together with the confirmed loss of C20 as CO2, this necessitates two catalytic cycles for carbon–carbon bond scission and γ‐lactone formation. The ability of CYP112 to hydroxylate the δ‐lactone form of GA15, shown by the labeling studies, is consistent with the implied use of a further oxygenated heterocycle in the final conversion of GA24 into GA9, with the partial labeling of GA9, thus demonstrating that CYP112 partitions its reactants between two diverging mechanisms.

Comments

This is the peer-reviewed version of the following article: Nagel, Raimund, and Reuben J. Peters. "Diverging Mechanisms: Cytochrome‐P450‐Catalyzed Demethylation and γ‐Lactone Formation in Bacterial Gibberellin Biosynthesis." Angewandte Chemie International Edition 57, no. 21 (2018): 6082-6085, which has been published in final form at DOI: 10.1002/anie.201713403. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. Posted with permission.

Copyright Owner

Wiley-VCH VerlagGmbH &Co. KGaA,Weinheim

Language

en

File Format

application/pdf

Published Version

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