Slow-Starter Enzymes: Role of Active-Site Architecture in the Catalytic Control of the Biosynthesis of Taxadiene by Taxadiene Synthase.

Taxadiene synthase (TXS) catalyzes the formation of natural product taxa-4(5),11(12)-diene (henceforth taxadiene). Taxadiene is the precursor in the formation of Taxol, which is an important natural anticancer agent. In the current study, we present a detailed mechanistic view of the biosynthesis of taxadiene by TXS using a hybrid quantum mechanics-molecular mechanics potential in conjunction with free energy simulation methods.

Catalytic control in terpenoid cyclases: multiscale modeling of thermodynamic, kinetic, and dynamic effects.

In this Opinion we review some of the key work on terpene biosynthesis using multi-scale simulation approaches. Terpene synthases generate terpenes employing beautiful and rich carbocation chemistry, including highly specific ring formations, hydride, proton, methyl, and methylene migrations, followed by reaction quenching. In spite of the chemical finesse of these enzymes, terpene synthases are highly promiscuous.