Enzymatic synthesis of natural (+)-aristolochene from a non-natural substrate. Issue 97 (17th November 2016)

• Record Type: Journal Article
• Authors: Faraldos, Juan A.; Grundy, Daniel J.; Cascon, Oscar; Leoni, Stefano; van der Kamp, Marc W.; Allemann, Rudolf K.
• Is Part Of: Chemical communications. Volume 52:Issue 97(2016)
• Page Start: 14027
• Page End: 14030
• Publication Date: 2016-11-17
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/c6cc08164a
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Aristolochene synthase from Penicillium roqueforti converts 7-methylene-FDP, a substrate the enzyme never encounters in nature, to the natural product (+)-aristolochene. 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.