Comparative molecular field analysis (CoMFA) for sulfoxidation reactions in Mortierella isabellina ATCC 42613 and Helminthosporium sp. NRRL 4671.
Previous models for mechanisms of enzymatic sulfoxidation have been somewhat limited by a lack of knowledge of the essential features of substrate-enzyme versus product-enzyme relationships. Computerized methods for modeling ligand-protein (substrate-enzyme) interactions can overcome some of these limitations. Specifically, CoMFA (comparative molecular field analysis) provided a useful general approach in which to evaluate substrate-enzyme and product-enzyme relationships. The present investigation examined the relationship between substrate and product structure in predicting enantioselective sulfoxidation reactions using CoMFA for two species of microorganisms that have been used as models for mammalian metabolism, Mortierella isabellina and Helminthosporium sp. The overall enantioselectivity observed was based on the composite stereoselectivity of sulfoxide formation, sulfone formation (from the sulfoxide), and sulfoxide reduction back to the achiral substrate (sulfide).
Division of Medicinal Chemistry, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA.
Wen-Hsin
WH
Huang
Richard E
RE
Wilcox
Patrick J
PJ
Davis
D003198:Computer Simulation; D006375:Helminthosporium / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D020094:Mortierella / Q000378:metabolism*; D010084:Oxidation-Reduction; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013440:Sulfides / Q000737:chemistry / Q000378:metabolism; D013450:Sulfones / Q000737:chemistry / Q000378:metabolism; D013454:Sulfoxides / Q000737:chemistry / Q000378:metabolism; D013457:Sulfur Compounds / Q000737:chemistry* / Q000378:metabolism*
D013440:Sulfides; D013450:Sulfones; D013454:Sulfoxides; D013457:Sulfur Compounds