Changes in enzyme activities at the pyruvate node in glutamate-overproducing Corynebacterium glutamicum.
Glutamate is industrially produced by fermentation using Corynebacterium glutamicum. The key factor for efficient glutamate production by this microorganism has been considered to be a metabolic change at the 2-oxoglutarate dehydrogenase (ODH) branch point caused by a decrease in ODH activity under glutamate-overproducing conditions. However, this change would be insufficient because the ODH branch is merely the final branch in the glutamate biosynthetic pathway, and efficient glutamate production requires a balanced supply of acetyl-CoA and oxaloacetate (OAA), which are condensed to form a precursor of glutamate, namely, citrate. Therefore, there must be another (other) change(s) in metabolic flux. In this study, we demonstrated that a decrease in pyruvate dehydrogenase (PDH) activity catalyzes the conversion of pyruvate to acetyl-CoA. It is speculated that carbon flux from pyruvate to acetyl-CoA decreases under glutamate-overproducing conditions. Furthermore, an increase in pyruvate carboxylase (PC) activity, which catalyzes the reaction of pyruvate to OAA, is evident under glutamate-overproducing conditions, except under biotin-limited condition, which may lead to an increase in carbon flux from pyruvate to OAA. These data suggest that a novel metabolic change occurs at the pyruvate node, leading to a high yield of glutamate through adequate partitioning of the carbon flux.
Hasegawa
Takuo
T
Department of Green and Sustainable Chemistry, Tokyo Denki University, Tokyo, Japan.
Hashimoto
Ken-Ichi
K
Kawasaki
Hisashi
H
Nakamatsu
Tsuyoshi
T
D000105:Acetyl Coenzyme A / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D048230:Corynebacterium glutamicum / Q000201:enzymology*; D015536:Down-Regulation; D018698:Glutamic Acid / Q000096:biosynthesis*; D007218:Industrial Microbiology; D062907:Oxaloacetic Acid / Q000378:metabolism; D011766:Pyruvate Carboxylase / Q000378:metabolism*; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism*
D001426:Bacterial Proteins; D011768:Pyruvate Dehydrogenase Complex; D062907:Oxaloacetic Acid; D018698:Glutamic Acid; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D011766:Pyruvate Carboxylase