Metabolic engineering with terpene cyclases

The terpenoids are the largest and stereochemically diverse class of natural products, produced widely by plants. Terpene cyclases/synthases (TC/S) catalyze some of the most complex reactions in biology, capable of producing several thousand terpenes from a single substrate. We have determined the structures of a number of terpene cyclases, both in the free enzyme form and in complex with substrate analogues. These terpene cyclases were used in E. coli production platforms for terpene production and shown to direct the production of target terpenes at levels suitable for large-scale production. Results from structural, biochemical and computational studies of selected terpene cyclases and prospects for terpene production by metabolic engineering will be discussed.