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

The Saccharomyces cerevisiae ERG7Phe699 mutants produced one chair−chair−chair (C−C−C) and two chair−boat−chair (C−B−C) truncated tricyclic compounds, one tetracyclic 17α-exocyclic unrearranged intermediate, and two 17β-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 17α- and 17β-exocyclic side chain stereochemistry as well as in stabilizing the 6−6−5 tricyclic and the protosteryl C-17 cations.