Enhancement of Central Energy Metabolism, Microbial

Abstract

Improving the productivity of useful metabolites is critically important for industrializing the fermentation process. For this to be achieved, rapid conversion of the fermentation substrate into the target metabolite through enhancing central metabolism seems rational. Since the discovery of “Pasteur effects” more than 100 years ago, scientific evidence has accumulated, especially in the past 50 years, that central metabolism is under the control of the energy status of cells in vivo in such a way that catabolism is enhanced under energy‐deficient conditions. We investigated enhancement of fermentative production by boosting central metabolism through the manipulation of energy metabolism. We found that the introduction of defective F 1 Fo‐ATP synthase to impair oxidative phosphorylation is effective for enhancement of pyruvate production in Escherichia coli K‐12 (hereafter, we collectively define this mutation as the “ atp mutation” since F 1 Fo‐ATP synthase is encoded by the atp operon in E . coli K‐12). Clarification of the physiological alterations associated with the atp mutation revealed several interesting metabolic changes. Excellent producers of pyruvate and acetate have recently been engineered in E . coli K‐12, in which the atp mutation appears to contribute markedly to increase glucose consumption and metabolite production of the producers. Furthermore, the atp mutation was found to be effective for a gram‐positive industrially important bacterium, Corynebacterium glutamicum , in enhancing both glucose consumption and glutamic acid production. Elucidation of metabolic alterations in this atp mutant revealed significant differences from those found in the E . coli atp mutant, suggesting a diversity of adaptive responses to energy deficiency in different bacterial species.