On the Substrate Scope of Dimethylsulfonium Propionate Lyases toward Dimethylsulfoxonium Propionate Derivatives

Abstract

The six dimethylsulfonium propionate (DMSP) lyases DddQ, DddW, DddP, DddY, DddK and DddL catalyze the elimination of dimethyl sulfide from DMSP and can also cleave the marine metabolite dimethylsulfoxonium propionate (DMSOP) to DMSO and acrylate. In this study the potency of all six enzymes for the conversion of four DMSOP analogs with longer alkyl chains that were synthesized in three steps from 3-mercaptopropionic acid was investigated. For this purpose, the pH dependency of the enzyme reactions was determined, showing optimal conditions at pH 8 for all enzymes but DddP, for which an optimum of pH 6 was found. Efficient transformations were observed for DddQ, DddW, DddY and DddK, for which the Michaelis-Menten kinetics were determined for all four substrate analogs. HPLC analysis of the dialkylsulfoxides obtained with the most efficient enzyme DddW revealed that these compounds were obtained with a low to moderate enantiomeric excess (up to 25 % ee), demonstrating that this enzyme has a preference for one of the enantiomers of the DMSOP analogs.