An enzymatic process to alpha-ketoglutarate from L-glutamate: the coupled system L-glutamate dehydrogenase/NADH oxidase

alpha-Ketoglutarate, employed to treat mild chronic renal insufficiency, was obtained through enzymatic oxidation of monosodium glutamate (MSG) catalyzed by L-glutamate dehydrogenase (L-gluDH) coupled with NADH oxidase for the regeneration of NADH back to NAD(+). The irreversible reduction of molecular oxygen to water by NADH oxidase is demonstrated to drive oxidation of MSG to alpha-ketoglutarate to completion. L-gluDH was found to be inhibited by all three oxidative deamination products, alpha-ketoglutarate, NADH, and ammonia. As the pH in the current system was balanced by sodium, not ammonia, and NADH was recycled to NAD(+), inhibition of L-gluDH by alpha-ketoglutarate is believed to present the biggest challenge to an efficient process. In a batch experiment, we achieved a volumetric productivity of 1 g/(L(.)d). (C) 2004 Elsevier Ltd. All rights reserved