The enzyme mechanism of patchoulol synthase

Houchao Xu; Bernd Goldfuss; Gregor Schnakenburg; Jeroen S Dickschat

doi:10.3762/bjoc.18.2

The enzyme mechanism of patchoulol synthase

Beilstein J Org Chem. 2022 Jan 3:18:13-24. doi: 10.3762/bjoc.18.2. eCollection 2022.

Authors

Houchao Xu¹, Bernd Goldfuss², Gregor Schnakenburg³, Jeroen S Dickschat¹

Affiliations

¹ Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.
² Department of Chemistry, University of Cologne, Greinstraße 4, 50939 Cologne, Germany.
³ Institute of Inorganic Chemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.

Abstract

Different mechanisms for the cyclisation of farnesyl pyrophosphate to patchoulol by the patchoulol synthase are discussed in the literature. They are based on isotopic labelling experiments, but the results from these experiments are contradictory. The present work reports on a reinvestigation of patchoulol biosynthesis by isotopic labelling experiments and computational chemistry. The results are in favour of a pathway through the neutral intermediates germacrene A and α-bulnesene that are both reactivated by protonation for further cyclisation steps, while previously discussed intra- and intermolecular hydrogen transfers are not supported. Furthermore, the isolation of the new natural product (2S,3S,7S,10R)-guaia-1,11-dien-10-ol from patchouli oil is reported.

Keywords: DFT calculations; biosynthesis; enzyme mechanisms; isotopes; terpenes.

Grants and funding

This work was funded by the DFG (DI1536/7-2).