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

Juan A. Faraldos, Daniel J Grundy, Oscar Cascon, Stefano Leoni, Marc Van der Kamp, Rudolf K. Allemann

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)14027-14030
Number of pages4
JournalChemical Communications
Volume52
Issue number97
Early online date3 Nov 2016
DOIs
Publication statusPublished - 18 Dec 2016

Structured keywords

  • Bristol BioDesign Institute

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