Enzyme Mechanisms for Polycyclic Triterpene Formation.

The mechanisms by which triterpene cyclases transform olefins into complex and biologically important polycyclic products have fueled nearly half a century of intense research. Recent chemical and biological studies, together with previous findings, provide intriguing new insights into the enzymatic mechanism of triterpene formation and form a surprisingly detailed picture of these elegant catalysts. It can be concluded that the role of the oxidosqualene cyclases involves protection of the intermediate carbocation against addition of water or deprotonation by base, thereby allowing the shift of the hydride and methyl groups along a thermodynamically and kinetically favorable cascade. Key questions in the areas of structural biology, site-directed mutagenesis, and directed evolution are apparent, now that the first structure of a triterpene cyclase is known.