Chiral gamma-aminobutyric acids (GABAs) represent abundantly prescribed drugs, which are broadly applied as anticonvulsants, antidepressants and for the treatment of neuropathic pain. With the incorporation of more population to western-based style in the coming decades, there is a need of developing and producing pharmaceutically active GABAs and similar or generic drugs for higher number of consumers. Supported by an ERC-PoC grant, Prof. Poelarends and his team have developed an efficient enzymatic cascade process for the step-economic production of various stable and practical GABA precursors, starting from simple chemical building blocks. This novel synthetic route highlights a highly regio- and stereoselective carbon-carbon bond-forming step catalyzed by a newly engineered artificial Michaelase. The applied strategy further exploits a natural oxidoreductase specifically chosen for its broad non-natural substrate promiscuity, as well as an efficient cofactor-recycling system. To enable the next step towards commercialization, a strong and attractive technology portfolio is currently being assembled in collaboration with industrial partners.
