Chemically Modified Mutants, a Marriage of Chemical Modification and Protein Engineering

Chemically Modified Mutants, a Marriage of Chemical Modification and Protein Engineering 

Expansion of Substrate Specificity with Protein Engineering and Directed Evolution 

To expand the substrate specificity and stereoselectivity of the aldolase DERA (2-deoxyribose-5-phosphate aldolase, E.C. 4.1.2.4), both site-specific mutagenesis and random mutagenesis have been investigated (DeSantis, 2003). The goal was to extend substrate specificity to the unnatural non-phosphorylated substrate, D-2-deoxyribose. 

Five amino acid residues were picked for mutation, based on the 3D crystal structure of DERA complexed with its natural substrate. 

The S238D variant was successful in three different ways  

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