Cofactor regeneration

One of the longstanding challenges in the synthesis of pharmaceuticals, cosmetics and food additives is the continuous regeneration of molecules called cofactors that permit the synthesis through inexpensive and environmentally friendly biocatalytic processes.

Now, a team of researchers from the University of Illinois at Urbana-Champaign and the Universite Paul Sabatier in Toulouse, France, has developed a microreactor that efficiently regenerates cofactors through enzyme-catalysed reactions.

"Enzymes are nature's catalysts, but in some cases, enzymes can not prompt a speedy chemical reaction," said Paul Kenis, a professor of chemical and biomolecular engineering at Illinois and a researcher at the Beckman Institute for Advanced Science and Technology. "In those cases, one or more cofactors are required."

By continuously regenerating the required cofactors, the microreactor enables the desired biocatalytic processes. Kenis and his colleagues describe their work in a paper that has been accepted for publication in the Journal of the American Chemical Society.

The microreactor uses a Y-shaped microfluidic channel in which two liquid streams, a reactant stream and a buffer stream, merge and flow laminarly between two electrodes without mixing. By adjusting the flow rates of the two streams, the researchers can focus the reactant stream close to the cathode, and a normally unfavourable reaction equilibrium is driven into the desired direction of cofactor regeneration.

"In large batch reactors, a spontaneous reverse reaction prevents the regeneration of essential cofactors," Kenis said. "The absence of a bulk phase in our microreactor prevents the unwanted reverse reaction from occurring, while permitting continuous operation."

Using their microreactor, the researchers performed a model biocatalytic process by converting an achiral substrate (pyruvate) into a chiral product (L-lactate), using lactate dehydrogenase as the enzyme.

While further research is needed to improve the performance of individual microreactors, the present work shifts the emphasis from the longstanding problem of cofactor regeneration to a more tangible engineering challenge, Kenis said. "Now we need to integrate a large number of these microreactors in a recirculating system to enable the biocatalytic synthesis of chiral fine chemicals in larger quantities."