Issue 97, 2016

Enzymatic synthesis of natural (+)-aristolochene from a non-natural substrate

Abstract

The sesquiterpene cyclase aristolochene synthase from Penicillium roquefortii (PR-AS) has evolved to catalyse with high specificity (92%) the conversion of farnesyl diphosphate (FDP) to the bicyclic hydrocarbon (+)-aristolochene, the natural precursor of several fungal toxins. Here we report that PR-AS converts the unnatural FDP isomer 7-methylene farnesyl diphosphate to (+)-aristolochene via the intermediate 7-methylene germacrene A. Within the confined space of the enzyme's active site, PR-AS stabilises the reactive conformers of germacrene A and 7-methylene germacrene A, respectively, which are protonated by the same active site acid (most likely HOPPi) to yield the shared natural bicyclic intermediate eudesmane cation, from which (+)-aristolochene is then generated.

Graphical abstract: Enzymatic synthesis of natural (+)-aristolochene from a non-natural substrate

Supplementary files

Article information

Article type
Communication
Submitted
10 Oct 2016
Accepted
28 Oct 2016
First published
03 Nov 2016
This article is Open Access
Creative Commons BY license

Chem. Commun., 2016,52, 14027-14030

Enzymatic synthesis of natural (+)-aristolochene from a non-natural substrate

J. A. Faraldos, D. J. Grundy, O. Cascon, S. Leoni, M. W. van der Kamp and R. K. Allemann, Chem. Commun., 2016, 52, 14027 DOI: 10.1039/C6CC08164A

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