Alteration of the Substrate's Prefolded Conformation and Cyclization Stereochemistry of Oxidosqualene-Lanosterol Cyclase of Saccharomyces cerevisiae by Substitution at Phenylalanine 699

Abstract

The Saccharomyces cerevisiae ERG7(Phe699) mutants produced one chair-chair-chair (C-C-C) and two chair-boat-chair (C-B-C) truncated tricyclic compounds, one tetracyclic 17 alpha-exocyclic unrearranged intermediate, and two 17 beta-exocyclic truncated rearranged intermediates. These results provided direct evidence for the importance of the residue in affecting mechanistic transitions between C-B-C and C-C-C substrate conformation and between the 17 alpha- and 17 beta-exocyclic side chain stereochemistry as well as in stabilizing the 6 -6-5 tricyclic and the protosteryl C-17 cations.