Biocatalytic asymmetric phosphorylation of mevalonate

The excellent selectivity of the mevalonate kinase-catalyzed phosphorylation of mevalonate simplifies lengthy multi-step routes to (R)-mevalonate-5-phosphate to a one-step biocatalytic reaction, because the phosphate group can be transferred directly and without any additional reaction steps involving introduction and removal of protecting groups. By adjusting the required reaction time for complete conversion, the kinetic resolution of racemic mevalolactone can be easily used for the preparation of (S)-mevalonate and (R)-mevalonate-5-phosphate. A new recombinant mevalonate kinase has been prepared by the expression of the mevalonate kinase gene from the hyperthermophilic archaeon Thermococcus kodakarensis in Escherichia coli and by the subsequent purification. Direct quantitative ³¹P-NMR kinetic analysis has been utilized to characterize the enantioselectivity of the mevalonate kinase. This method is useful for determining the biocatalyst's utility for the synthesis of enantiomerically pure (R)-mevalonate-5-phosphate as well as for biocatalytic process development. This journal is