title: The 2-oxoglutarate supply exerts significant control on the lysine synthesis flux in Saccharomyces cerevisiae.
abstract: To determine the extent to which the supply of the precursor 2-oxoglutarate (2-OG) controls the synthesis of lysine in Saccharomyces cerevisiae growing exponentially in high glucose, top-down elasticity analysis was used. Three groups of reactions linked by 2-OG were defined. The 2-OG supply group comprised all metabolic steps leading to its formation, and the two 2-OG consumer groups comprised the enzymes and transporters involved in 2-OG transformation into lysine and glutamate and their further utilization for protein synthesis and storage. Various 2-OG steady-state concentrations that produced different fluxes to lysine and glutamate were attained using yeast mutants with increasing activities of Krebs cycle enzymes and decreased activities of Lys synthesis enzymes. The elasticity coefficients of the three enzyme groups were determined from the dependence of the amino acid fluxes on the 2-OG concentration. The respective degrees of control on the flux towards lysine (flux control coefficients) were determined from their elasticities, and were 1.1, 0.41 and -0.52 for the 2-OG producer group and the Lys and Glu branches, respectively. Thus, the predominant control exerted by the 2-OG supply on the rate of lysine synthesis suggests that over-expression of 2-OG producer enzymes may be a highly effective strategy to enhance Lys production.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, Mexico.
authors.forename: Héctor
authors.initials: H
authors.lastname: Quezada
authors.forename: Alvaro
authors.initials: A
authors.lastname: Marín-Hernández
authors.forename: Roberto
authors.initials: R
authors.lastname: Arreguín-Espinosa
authors.forename: Franklin D
authors.initials: FD
authors.lastname: Rumjanek
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno-Sánchez
authors.forename: Emma
authors.initials: E
authors.lastname: Saavedra
mesh_terms: D002952:Citric Acid Cycle / Q000235:genetics; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism*; D007700:Kinetics; D008239:Lysine / Q000096:biosynthesis*; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004798:Enzymes; D007656:Ketoglutaric Acids; D029701:Saccharomyces cerevisiae Proteins; D008239:Lysine
keywords: 2-oxoglutarate supply; elasticity analysis; glutamate biosynthesis; lysine biosynthesis; metabolic control analysis