Terpene Synthase Structure-Function

Project GoalsIntegrative approaches to tease out the determinants of product specificity in terpene synthases
FundingDepartment of Energy – Energy Biosciences Program
CollaboratorsSimone Raugei, Hoshin Kim – Pacific Northwest National Laboratory

Executive Summary

Terpene synthases convert a prenyl diphosphate of a specific chain length to the first pathway-specific (often cyclic) intermediate in the biosynthesis of each class of terpenoids.  While some terpene synthases are remarkably specific and generate only one product, others release a larger number of products from a common substrate, thus contributing to terpenoid chemical diversity. We are using data from sequence comparisons, crystal structures, and molecular dynamics simulations to develop an understanding of how specificity arises in terpene synthases. Based on these insights we are developing models with a longer term goal to be able to predict the function of terpene synthases.

Selected Recent Publications

Srividya N., Kim H., Simone R., Lange B.M. (2024) Chemical diversity in angiosperms− monoterpene synthases control complex reactions that provide the precursors for ecologically and commercially important monoterpenoids. Plant J. 119, 28-55.

Lange B.M., Srividya N. (2023) Cannabis monoterpene synthases: evaluating structure–function relationships. Phytochem. Rev. 22, 449-465.

Lange B.M., Srividya N., Lange I., Parrish A.N., Benzenberg L.R., Pandelova I., Vining K.J., Wüst M. (2023) Biochemical basis for the formation of organ-specific volatile blends in mint. Front. Plant Sci. 14, 1125065.

Kim H., Srividya N., Lange I., Huchala E.W., Ginovska B., Lange B.M., Raugei S. (2022) Determinants of selectivity for the formation of monocyclic and bicyclic products in monoterpene synthases. ACS Catal. 12, 7453-7469.

Srividya N., Lange I., Richter J.K., Wüst M., Lange B.M. (2022). Selectivity of enzymes involved in the formation of opposite enantiomeric series of p-menthane monoterpenoids in peppermint and Japanese catnip. Plant Sci. 314 , 111119

Srividya N., Lange I., Lange B.M. (2020) Determinants of enantiospecificity in limonene synthases. Biochemistry 59, 1661-1664

Lange B.M., Srividya N. (2019) Enzymology of monoterpene functionalization in glandular trichomes. J. Exp. Bot., 70, 1095-1108.

Srividya N., Lange I., Lange B.M. (2016) Generation and functional evaluation of designer monoterpene synthases. Methods Enzymol. 576, 147-165

Srividya N., Davis E.M., Croteau R.B., Lange B.M. (2015) Functional analysis of (4S)-limonene synthase mutants reveals determinants of catalytic outcome in a model monoterpene synthase. Proc. Natl. Acad. Sci. USA 112, 3332-3337