The cysteine 703 to isoleucine or histidine mutation of the oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae generates an iridal-type triterpenoid

Abstract The Cys703 to Ile or His mutation within Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase ERG7 (ERG7 C703I/H ) generates an unusual truncated bicyclic rearranged intermediate, (8 R ,9 R ,10 R )-polypoda-5,13 E ,17 E ,21-tetraen-3β-ol, related to iridal-skeleton triterpenoid. Numerous oxidosqualene-cyclized truncated intermediates, including tricyclic, unrearranged tetracyclic with 17α/β exocyclic hydrocarbon side chain, rearranged tetracyclic, and chair–chair–chair tricyclic intermediates (compounds 3 – 9 ), were also isolated from the ERG7 C703X site-saturated mutations or the ERG7 F699T/C703I double mutation, indicating the functional role of the Cys703 residue in stabilizing the bicyclic C-8 cation and the rearranged intermediate or interacting with Phe699, and opened a new avenue of engineering ERG7 for producing biological active agents.