Issue 97, 2016

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


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

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Article information

Article type
10 Oct 2016
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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