title: Flux to acetate and lactate excretions in industrial fermentations: physiological and biochemical implications.
abstract: The efficiency of carbon conversion to biomass and desirable end products in industrial fermentations is diminished by the diversion of carbon to acetate and lactate excretions. In this study, the use of prototrophic and mutant strains of Escherichia coli, as well as enzyme active site directed inhibitors, revealed that flux to acetate excretion is physiologically advantageous to the organism as it facilitates a faster growth rate (mu) and permits growth to high cell densities. Moreover, the abolition of flux to acetate excretion was balanced by the excretion of lactate as well as 2-oxoglutarate, isocitrate and citrate, suggesting a 'bottle-neck' effect at the level of 2-oxoglutarate in the Krebs cycle. It is proposed that the acetate excreting enzymes, phosphotransacetylase and acetate kinase, constitute an anaplerotic loop or by-pass, the primary function of which is to replenish the Krebs cycle with reduced CoA, thus relieving the bottle-neck effect at the level of 2-oxoglutarate dehydrogenase. Furthermore, flux to lactate excretion plays a central role in regenerating proton gradient and maintaining the redox balance within the cell. The long-held view that flux to acetate and lactate excretions is merely a function of an 'over-flow' in central metabolism should, therefore, be re-evaluated.
authors.affiliation: Applied Microbiology and Biotechnology Group, University School of Life Sciences, Napier University, EH10 5DT, Edinburgh, UK. m.el-mansi@napier.ac.uk
authors.forename: Mansi
authors.initials: M
authors.lastname: El-Mansi
mesh_terms: D000084:Acetate Kinase / Q000502:physiology; D000085:Acetates / Q000378:metabolism*; D019343:Citric Acid / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D005942:Gluconates / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007523:Isocitrates / Q000378:metabolism; D007655:Ketoglutarate Dehydrogenase Complex / Q000502:physiology; D007656:Ketoglutaric Acids / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D010084:Oxidation-Reduction; D010709:Phosphate Acetyltransferase / Q000502:physiology; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism
chemical_list: D000085:Acetates; D004791:Enzyme Inhibitors; D005942:Gluconates; D007523:Isocitrates; D007656:Ketoglutaric Acids; D011773:Pyruvates; D019343:Citric Acid; D019344:Lactic Acid; C017092:bromopyruvate; D019289:Pyruvic Acid; C034219:isocitric acid; D007655:Ketoglutarate Dehydrogenase Complex; D010709:Phosphate Acetyltransferase; D000084:Acetate Kinase; D005947:Glucose; C030691:gluconic acid; D003065:Coenzyme A