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Updated: Mar 12, 2026

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Enzymatic synthesis of natural (+)-aristolochene from a non-natural substrate
Juan A Faraldos1, Daniel J Grundy1, Oscar Cascon1
1School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UK. AllemannRK@cardiff.ac.uk.
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.
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