Issue 48, 2021

Computational studies on the sterol-like cyclization of a monodomain class II terpene cyclase

Abstract

Recently the first example of a class II terpene cyclase comprised of only a single domain was reported. Class II synthases are a diverse group of enzymes that catalyze exceptionally complex reactions, including the remarkable cyclization of steroids. This discovery of a single-domain enzyme being able to catalyze a steroid-like product contradicted the long-held tenet that complex class II cyclizations required double-domain enzymes. The proposed mechanism for the sterol-like cyclization of a monodomain class II terpene cyclase was studied computationally by using density functional theory (DFT). The complete pathway for the conversion of 5-geranyl-3,4-dihydroxybenzoate to the steroid-like pentacyclic product merosterolic acid A was elucidated. The formation of a tricyclic carbocation intermediate with three cyclohexane rings was found to be a concerted, but asynchronous, cyclization. The formation of the fourth ring proceeds with a low energy activation Friedel–Crafts reaction. Subsequent deprotonation of this pentacyclic system gave as the final product merosterolic acid. The overall conversion was found to be highly exothermic due to the conversion of three C–C double bonds to C–C single bonds.

Graphical abstract: Computational studies on the sterol-like cyclization of a monodomain class II terpene cyclase

Supplementary files

Article information

Article type
Paper
Submitted
14 out 2021
Accepted
19 nov 2021
First published
19 nov 2021

Org. Biomol. Chem., 2021,19, 10647-10651

Computational studies on the sterol-like cyclization of a monodomain class II terpene cyclase

B. A. Hess, J. Piel and L. Smentek, Org. Biomol. Chem., 2021, 19, 10647 DOI: 10.1039/D1OB02018H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements