Structural highlights
Function
[MDH_CORGL] Catalyzes the reversible oxidation of malate to oxaloacetate. Exhibits higher catalytic efficiency for oxaloacetate reduction than for malate oxidation in vitro. Almost equally active both for NADH and NADPH on the bases of the kcat values at pH 6.5, but catalytic efficiency for oxaloacetate reduction is 50-fold higher with NADH.[1]
Publication Abstract from PubMed
Succinic acid (SA), a dicarboxylic acid of industrial importance, can be efficiently produced by metabolically engineered Mannheimia succiniciproducens. Malate dehydrogenase (MDH) is one of the key enzymes for SA production, but has not been well characterized. Here we report biochemical and structural analyses of various MDHs and development of hyper-SA producing M. succiniciproducens by introducing the best MDH. Corynebacterium glutamicum MDH (CgMDH) shows the highest specific activity and least substrate inhibition, whereas M. succiniciproducens MDH (MsMDH) shows low specific activity at physiological pH and strong uncompetitive inhibition toward oxaloacetate (ki of 67.4 and 588.9 muM for MsMDH and CgMDH, respectively). Structural comparison of the two MDHs reveals a key residue influencing the specific activity and susceptibility to substrate inhibition. A high-inoculum fed-batch fermentation of the final strain expressing cgmdh produces 134.25 g L(-1) of SA with the maximum productivity of 21.3 g L(-1) h(-1), demonstrating the importance of enzyme optimization in strain development.
Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase.,Ahn JH, Seo H, Park W, Seok J, Lee JA, Kim WJ, Kim GB, Kim KJ, Lee SY Nat Commun. 2020 Apr 23;11(1):1970. doi: 10.1038/s41467-020-15839-z. PMID:32327663[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Genda T, Nakamatsu T, Ozak H. Purification and characterization of malate dehydrogenase from Corynebacterium glutamicum. J Biosci Bioeng. 2003;95(6):562-6. PMID:16233457
- ↑ Ahn JH, Seo H, Park W, Seok J, Lee JA, Kim WJ, Kim GB, Kim KJ, Lee SY. Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase. Nat Commun. 2020 Apr 23;11(1):1970. doi: 10.1038/s41467-020-15839-z. PMID:32327663 doi:http://dx.doi.org/10.1038/s41467-020-15839-z
