CRYSTALLOGRAPHIC ANALYSIS OF TERPENE CYCLASES

萜烯环化酶催化无环烃的转化

Terpene cyclases catalyze the conversion of acyclic hydrocarbon diphosphates to a wide variety of cyclic skeletons, via readily rearranging carbocation intermediates. The enormous array of possible terpenoid structures provides a natural library of compounds to screen for pharmaceutical and agricultural applications, and natural and engineered terpene cyclases could provide readily available in vitro sources of these compounds. In order to better understand the machinery of terpene cyclases and how to re-engineer them, we have determined the structure of 5-epi-aristolochene synthase (TEAS), a terpene cyclase from tobacco. Based on this structure, we have designed several mutant enzymes, which have new substrate and product specificities. We are now further examining the determinants of specificity in TEAS and working to determine crystal structures of other terpene cyclases.