Differential Stereocontrolled Formation of Tricyclic Triterpenes by Mutation of Tyrosine 99 of the Oxidosqualene-Lanosterol Cyclase from Saccharomyces cerevisiae

The function of the Tyr99 residue from Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase (ERG7) was analyzed by constructing deletion and site-saturated mutants. Two truncated intermediates, (13αH)-isomalabarica-14Z,17E,21-trien-3β-ol and (13αH)-isomalabarica-14E,17E,21-trien-3β-ol, were isolated from the ERG7Y99X mutants. These results suggest that the functional role of ERG7Y99 is to affect both chair–boat 6–6–5 tricyclic Markovnikov C-14 cation stabilization and thestereochemistry of the protons at the C-15 position for subsequent deprotonation. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)