From functional plasticity of two diterpene synthases (IrTPS2/IrKSL3a) to enzyme evolution.

ABSTRACT: Terpenoids are an intriguing class of natural products with diverse structures and biological activities whose complexity stems, in large part, from terpene synthases (TPSs). These enzymes catalyze carbocationic cascade reactions wherein the groups responsible for quenching the final carbocation is generally not well known. IrKSL3a and IrTPS2 from Isodon rubescens share 98% sequence homology but use distinct quenching strategies, with IrKSL3a catalyzing direct deprotonation to generate the olefin isopimaradiene while IrTPS2 adds water to yield the hydroxylated nezukol. In this work, we discovered a threonine and serine that hydrogen-bond the water to be added in IrTPS2. Site-directed mutagenesis and multiscale QM/MM simulations of modeled structures further reveal that binding of th

SUBMITTER: Jin B 

PROVIDER: S-EPMC12312555 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature