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

Faraldos, Juan, Grundy, Daniel, Cascon Salgado, Oscar, Leoni, Stefano, van der Kamp, Marc W and Allemann, Rudolf ORCID: https://orcid.org/0000-0002-1323-8830 2016. Enzymatic synthesis of natural (+)-aristolochene from a non-natural substrate. Chemical Communications 52 (97) , pp. 14027-14030. 10.1039/C6CC08164A

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry
Publisher:	RSC Publishing
ISSN:	1359-7345
Funders:	BBSRC, EPSRC
Date of First Compliant Deposit:	23 November 2016
Date of Acceptance:	28 October 2016
Last Modified:	02 May 2023 17:26
URI:	https://orca.cardiff.ac.uk/id/eprint/96390

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