Efficient production of gamma‐aminobutyric acid by engineered Saccharomyces cerevisiae with glutamate decarboxylases from Streptomyces

Abstract Gamma‐aminobutyric acid (GABA) is an industrially valuable natural product. This study was aimed to establish an efficient food‐grade production process of GABA by engineering Saccharomyces cerevisiae that is generally recognized as safe (GRAS). GABA can be produced by catalytic decarboxylation of l ‐glutamate ( l ‐Glu) by glutamate decarboxylase (GAD, EC4.1.1.15). Two GADs, SsGAD from Streptomyces sp . MJ654‐NF4 and ScGAD from Streptomyces chromofuscus ATCC 49982, were heterologously expressed in S. cerevisiae BJ5464. The engineered yeast strains were used as whole‐cell biocatalysts for GABA production. S. cerevisiae BJ5464/SsGAD exhibited significantly higher efficient catalytic activity than that of S. cerevisiae BJ5464/ScGAD. The optimal bioconversion system consisted of a cell density of OD 600 30, 0.1 M l ‐Glu, and 0.28 mM pyridoxal phosphate in 0.2 M Na 2 HPO 4 –citric acid buffer with pH 5.4, and the reactions were performed at 50 °C for 12 H. S. cerevisiae BJ5464/SsGAD cells can be reused, and the accumulated GABA titer reached 62.6 g/L after 10 batches with an overall molar conversion rate of 60.8 mol%. This work thus provides an effective production process of GABA using engineered yeast for food and pharmaceutical applications.