Researchers in Japan have changed the catalytic function of an enzyme by switching just one of its amino acids. 

Hiromichi Ohta and colleagues at Keio University, Yokohama, Japan, prepared a mutated version of an enzyme called AMDase, different from the wild-type by just one cysteine amino acid in its core structure. They found that this single mutation gave the enzyme a new function - the enzyme now catalysed a racemase reaction, distinctly different from its normal decarboxylase reaction. 

The group's first clue that this mutation might work came from the similarity of the two enzymes AMDase and glutamate racemase. Both enzymes contain a cysteine amino acid at the same position in their active sites, known to be important in controlling the intermediate step of their reactions. Also, both create an intermediate product called an enolate. However, an additional cysteine seems to be involved in glutamate racemase's mechanism. The AMDase mutant made by Ohta's team contains this additional cysteine residue in place of a glycine. This is the first report of a single mutation to change a decarboxylase to a racemase, said Ohta. 

It is well established that enzymes can be used in organic synthesis, and redesigning them can improve their activity. Examining the common mechanistic points of apparently distinct enzymatic reactions is an important consideration for redesign, said Ohta. 

Kurt Faber, an expert in biocatalysis from the University of Graz, Austria, sees enzyme design as an important way to develop new biocatalysts. 'The construction of a racemase from a decarboxylase by a single point mutation is a clever application of this concept,' said Faber. 

Katherine Vickers