Engineering terpene synthases and their substrates for the biocatalytic production of terpene natural products and analogues.

Terpene synthases produce a wide number of hydrocarbon skeletons by controlling intramolecular rearrangements of allylic pyrophosphate subtrates reactive carbocation intermediates. Here we review recent research focused on engineering terpene synthases and modifying their substrates to rationally manipulate terpene catalyisis. Molecular dynamic simulations and solid state X-ray crystallography are powerful techniques to identify substrate binding modes, key active site residues for substrate folding, and the location of active site water.