6ITL

Crystal structure of malate dehydrogenase from Mannheimia succiniciproducens in complex with NAD

Summary for 6ITL

• Entry DOI: 10.2210/pdb6itl/pdb
• Descriptor: Malate dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: dehydrogenase, nucleotide binding, oxidoreductase
• Biological source: Mannheimia succiniciproducens (strain MBEL55E)
• Total number of polymer chains: 1
• Total formula weight: 34281.10

Authors

Seo, H.,Kim, K.-J. (deposition date: 2018-11-23, release date: 2019-11-27, Last modification date: 2023-11-22)

Primary citation

Ahn, J.H.,Seo, H.,Park, W.,Seok, J.,Lee, J.A.,Kim, W.J.,Kim, G.B.,Kim, K.J.,Lee, S.Y.
Enhanced succinic acid production by Mannheimia employing optimal malate dehydrogenase.
Nat Commun, 11:1970-1970, 2020

PubMed Abstract: 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 μM 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 of SA with the maximum productivity of 21.3 g L h, demonstrating the importance of enzyme optimization in strain development.

PubMed: 32327663
DOI: 10.1038/s41467-020-15839-z

Experimental method

X-RAY DIFFRACTION (1.97 Å)