Bacterial diterpene synthases prenylate small molecules.

ABSTRACT: The biosynthesis of terpenoid natural products begins with a carbocation-based cyclization or prenylation reaction. While these reactions are mechanistically similar, there are several families of enzymes, namely terpene synthases and prenyltransferases, that have evolved to specifically catalyze terpene cyclization or prenylation reactions. Here, we report that bacterial diterpene synthases, enzymes that are traditionally considered to be specific for cyclization, are capable of efficiently catalyzing both diterpene cyclization and the prenylation of small molecules. We investigated this unique dual reactivity of terpene synthases through a series of kinetic, biocatalytic, structural, and bioinformatics studies. Overall, this study unveils the ability of terpene synthases to catalyze C-, N-, O-, and S-prenylation on small molecules, proposes a substrate decoy mechanism for prenylation by terpene synthases, supports the physiological relevance of terpene synthase-catalyzed prenylation in vivo, and addresses questions regarding the evolution of prenylation function and its potential role in natural products biosynthesis.

SUBMITTER: Xu B 

PROVIDER: S-EPMC8594881 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature