Robust production of gamma-amino butyric acid using recombinant Corynebacterium glutamicum expressing glutamate decarboxylase from Escherichia coli

A new metabolic route for the production of gamma-aminobutyric acid by Corynebacterium glutamicum from glucose

“…As opposed to α-decarboxylation of glutamate to GABA by heterologous expression of a glutamate decarboxylase gene in a glutamate-producing strain (Choi et al 2015;Okai et al 2014;Shi et al 2013;Takahashi et al 2012;Wang et al 2015), heterologous expression of patA and patD from E. coli in a putrescine producer strain enabled GABA production via putrescine by glucose fermentation. C. glutamicum is not only a suitable host for production of glutamate, but also of putrescine and GABA.…”

“…In the approach described here, GABA was produced by recombinant C. glutamicum from glucose with a volumetric productivity of 0.31 g L −1 h −1 , which is the highest reported volumetric productivity in shake flasks for GABA production in C. glutamicum. In comparison, volumetric productivities for GABA producing strains overexpressing a glutamate decarboxylase gene from either E. coli or Lactobacillus brevis were between 0.09 and 0.26 g L −1 h −1 (Choi et al 2015;Okai et al 2014;Shi et al 2013;Takahashi et al 2012). This may be explained at least in part by the observation that GABA already accumulated in the exponential growth phase when produced via putrescine (Fig.…”

“…As C. glutamicum wild type is not known to synthesize GABA as intermediate or product, GABA production by C. glutamicum from glucose requires enzymes from heterologous sources, such as glutamate decarboxylase for direct conversion of glutamate to GABA (Choi et al 2015;Okai et al 2014;Shi et al 2013;Takahashi et al 2012). Since putrescine degradation proceeds via GABA in enteric bacteria, it was tested if the respective enzymes may be used to convert putrescine-producing C. glutamicum strains to GABA-producing strains.…”

“…However, production of GABA by these bacteria does not proceed from glucose but requires addition of glutamate to the culture medium . Fermentative production of GABA from glucose without the requirement to add l-glutamate was achieved by engineering Corynebacterium glutamicum, a natural l-glutamate producer (Choi et al 2015;Okai et al 2014;Shi et al 2013;Takahashi et al 2012;Wang et al 2015). The workhorse C. glutamicum is an intensively studied Gram-positive soil bacterium that has for decades been used for the safe production of amino acids (Eggeling and Bott 2005;Wendisch 2007;Yukawa and Inui 2013).…”

“…pyridoxal 5′-phosphate-dependent enzyme catalyzing the α-decarboxylation of glutamate to GABA (Takahashi et al 2012). In biotechnology, GABA may be produced by lactic acid bacteria, which usually possess an endogenous GAD.…”