Promiscuous protease-catalyzed aldol reactions: A facile biocatalytic protocol for carbon-carbon bond formation in aqueous media

Several proteases, especially pepsin, were observed to directly catalyze asymmetric aldol reactions. Pepsin, which displays well-documented proteolytic activity under acidic conditions, exhibited distinct catalytic activity in a crossed alclol reaction between acetone and 4-nitrobenzaldehyde with high yield and moderate enantioselectivity. Fluorescence experiments indicated that under neutral pH conditions, pepsin maintains its native conformation and that the natural structure plays an important role in biocatalytic promiscuity. Moreover, no significant loss of enantioselectivity was found even after four cycles of catalyst recycling, showing the high stability of pepsin under the selected aqueous reaction conditions. This case of biocatalytic promiscuity not only expands the application of proteases to new chemical transformations, but also could be developed into a potentially valuable method for green organic synthesis. (C) 2010 Elsevier B.V. All rights reserved.