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Understanding Product Selectivity of Monoterpene Synthases Using Atomistic Simulations


EMSL Project ID
60341

Abstract

Monoterpene synthases (MTSs) catalyze the biosynthesis of monoterpenes, which play a pivotal role in plant-plant communications as well as key ingredients for many industrial applications including flavor additives, fragrance, and biofuels. MTSs control challenging reactions that involve highly reactive carbocations in a selective and stereospecific manner. However, despite their versatility, a general understanding of mechanistic underpinnings of selectivity and specificity of MTSs remains elusive. In this proposed research project, we plan to apply state-of-the-art computational tools for atomistic simulations of enzymatic systems to understand (1) how exquisite electrostatic and steric confinement can control highly reactive carbocationic intermediates in a specific manner, (2) how architecture and chemical properties of the active site can steer the reaction sequences, and (3) what active site residues play a crucial role in the selectivity at different reaction stages. This research is expected to give a more complete picture of the active site chemistry of MTSs as well as provide a guide to design the variants with the desired specificity, which can give direct positive impacts to many applications.

Project Details

Project type
Large-Scale EMSL Research
Start Date
2022-10-01
End Date
N/A
Status
Active

Team

Principal Investigator

Hoshin Kim
Institution
Pacific Northwest National Laboratory

Co-Investigator(s)

Bernd Markus Lange
Institution
Washington State University

Narayanan Srividya
Institution
Washington State University

Simone Raugei
Institution
Pacific Northwest National Laboratory

Bojana Ginovska
Institution
Pacific Northwest National Laboratory