Selectivity of enzymes involved in the formation of opposite enantiomeric series of p-menthane monoterpenoids in peppermint and Japanese catnip

Srividya, Narayanan; Lange, Iris; Richter, Jana K.; Wüst, Matthias; Lange, B. Markus

doi:10.1016/j.plantsci.2021.111119

Title: Selectivity of enzymes involved in the formation of opposite enantiomeric series of p-menthane monoterpenoids in peppermint and Japanese catnip

Journal Article · Thu Nov 18 00:00:00 EST 2021 · Plant Science

DOI:https://doi.org/10.1016/j.plantsci.2021.111119· OSTI ID:1868339

^[1]; Lange, Iris ^[1];

^[2]; Wüst, Matthias ^[3]; Lange, B. Markus ^[1]

Washington State Univ., Pullman, WA (United States)
Washington State Univ., Pullman, WA (United States); Rheinische Friedrich-Wilhelms-Univ. Bonn (Germany)
Rheinische Friedrich-Wilhelms-Univ. Bonn (Germany)

Peppermint (Mentha x piperita L.) and Japanese catnip (Schizonepeta tenuifolia (Benth.) Briq.) accumulate p-menthane monoterpenoids with identical functionalization patterns but opposite stereochemistry. In the present study, we investigate the enantioselectivity of multiple enzymes involved in monoterpenoid biosynthesis in these species. Based on kinetic assays, mint limonene synthase, limonene 3-hydroxylase, isopiperitenol dehydrogenase, isopiperitenone reductase, and menthone reductase exhibited significant enantioselectivity toward intermediates of the pathway that proceeds through (-)-4S-limonene. Limonene synthase, isopiperitenol dehydrogenase and isopiperitenone reductase of Japanese catnip preferred intermediates of the pathway that involves (+)-4R-limonene, whereas limonene 3-hydroxylase was not enantioselective, and the activities of pulegone reductase and menthone reductase were too low to acquire meaningful kinetic data. Molecular modeling studies with docked ligands generally supported the experimental data obtained with peppermint enzymes, indicating that the preferred enantiomer was aligned well with the requisite cofactor and amino acid residues implicated in catalysis. A striking example for enantioselectivity was peppermint (-)-menthone reductase, which binds (-)-menthone with exquisite affinity but was predicted to bind (+)-menthone in a non-productive orientation that positions its carbonyl functional group at considerable distance to the NADPH cofactor. Here, the work presented here lays the groundwork for structure-function studies aimed at unraveling how enantioselectivity evolved in closely related species of the Lamiaceae and beyond.

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Research Organization:: Washington State Univ., Pullman, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Natural Science Foundation of China (NSFC)

Grant/Contract Number:: SC0001553

OSTI ID:: 1868339

Journal Information:: Plant Science, Vol. 314; ISSN 0168-9452

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Title: Selectivity of enzymes involved in the formation of opposite enantiomeric series of p-menthane monoterpenoids in peppermint and Japanese catnip

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