A comparative molecular field analysis of the biotransformation of sulfides by Rhodococcus erythropolis

A comparative molecular field analysis (CoMFA) was used to model the efficacy with which the Rhodococcus erythropolis mono-oxygenase, DszC, catalyzes the enantioselective sulfoxidation of a broad range of substrates. Experimentally determined values of both the yield and enantiomeric excess for this reaction were employed to create these CoMFA models. A highly predictive CoMFA model was constructed for the prediction of enantiomeric excess of the sulfoxide product. The predictive ability of the model was demonstrated by both cross-validation of the training set (q2 = 0.74) and for an external test set of substrates. The enantiomeric excesses of the members of the test set, which also included two amino acid sulfides that were structurally distinct from the membership of the training set, were predicted well by the CoMFA model. Product yield was not modelled well by any CoMFA model. Different models comparing the likely bioactive conformations of the substrates suggest that most compounds assume an ‘extended’ conformation upon binding. Contour diagrams illustrating significant substrate–enzyme interactions suggest that the model, which predicts the enantiomeric excess, is consistent with previous conclusions regarding the effect of various substrate substitutions on the enantiopurity of the product of the biotransformation.