MOLECULAR-CLONING OF THE HUMAN GENE ENCODING LANOSTEROL SYNTHASE FROMA LIVER CDNA LIBRARY

Lanosterol synthase [(S)-2,3-epoxysqualene mutase (cyclizing, lanoster ol forming), EC 5.4.99.7] catalyzes the cyclization of (S)-2,3-oxidosq ualene to lanosterol in the reaction that forms the sterol nucleus. We report herein the cloning and characterization of the human gene (OSC ) encoding lanosterol synthase, a predicted 83 kDa protein of 732 amin o acids. The deduced amino acid sequence is 36-40% identical to known yeast and plant homologues and 83% identical to Rattus norvegicus lano sterol synthase. The new gene was shown to encode lanosterol synthase. The yeast lanosterol synthase deficient mutant SMY8 was complemented by the human gene, and a cell-free homogenate of SMY8 expressing the h uman gene was shown to convert 2,3-oxidosqualene to lanosterol. (C) 19 95 Academic Press, Inc.