Previous work suggested that the restriction in donor substrate scope of DERA was possibly due to steric constraints in the active site . Moreover, the substrate scope of fructose-6-phosphate aldolase (FSA) was greatly ex-panded by a "minimalist protein engineering" approach increasing space in the active site . We initially decided to focus on a similar strategy, generating mutations in the active site of DERA with the intention of enlarging the binding pocket for the donor substrate. The previously reported crystal structure of E. coli DERA (PDB =1JCL) , which contains the linear aldol product bound to the catalytic lysine residue, was used to identify six active site residues in close proximity to the 2-position of the final product. These residues were mutated to alanine and the resulting variants screened for activity against a broad panel of aldehyde donor substrates (Figure ). *For FSA the opposite stereochemistry at C2 is generated to the stereochemistry shown.