MEANS AND METHODS FOR SYNTHESIZING PRECURSORS OF Y-AMINOBUTYRIC ACID (GABA) ANALOGS

The invention relates to the fields of drug development and biocatalysis, more specifically to a biocatalytic route for asymmetric synthesis of precursors of y-aminobutyric acid (GABA) analogs. Provided is an isolated mutant 4-oxalocrototonate tautomerase (4-OT) enzyme comprising the following mutations (i) leucine at position 8 substituted with a tyrosine (L8Y) or a phenylalanine (L8F); (ii) methionine at position 45 substituted with a tyrosine (M45Y); and (iii) phenylalanine at position 50 substituted with an alanine (F50A), wherein the positions are numbered according to the amino acid sequence of 4-OT of Pseudomonas putida. Also provided is a method for the synthesis of a precursor for the pharmaceutically relevant enantiomer of a GABA analog, comprising (i) providing a y-nitroaldehyde using the 4-OT mutant enzyme, followed by (ii) subjecting the thus obtained y-nitroaldehyde to an enzymatic oxidation reaction catalyzed by an aldehyde dehydrogenase (EC 1.2.1.3).