Maintaining maximal metabolic flux by gene expression control
Fig 2
Four well-characterised metabolic pathways in which a metabolite binds to a transcription factor (TF) to influence gene expression. The qORAC framework applies to each of them: in each case, the qORAC formalism gives rise to the enzyme synthesis rates that steer the metabolic pathway to maximal metabolic rates that are robust to changes in the external concentration (external with respect to the pathway). (A) The lac operon in E. coli, with sensor Allolactose binding to LacI; (B) The galactose uptake system in yeast, with sensor internal galactose binding to gal3p; (C) The control of glycolytic enzymes via sensors FBP (binding to Cra), and cAMP (binding to Crp); (D) The control of the L-Tryptophan biosynthesis pathway by the amino acid binding to TrpR; (E) The general scheme of a qORAC-steered pathway. Abbreviations:Lacout, external lactose; Allolac, allolactose; αKG, α-ketoglutarate;Galout, external galactose; Galin, internal galactose; Gal-1P, galactose-1-phosphate; Glc-1P, glucose-1-phosphate; UDP-Glc, uridine-diphosphate-glucose; UDP-Gal, uridine-diphosphate-galactose; Glu, glucose; FBP, fructose-1,6-biphosphate; PEP, phosphoenolpyruvate; PYR, pyruvate; cAMP, cyclic AMP; ATP, adenosine-triphosphate; Cho, chorismate; Ant, Anthranilate; NAnt, N-(5’-phosphoribosyl)-anthranilate; ECP1P, Enol-1-0-carboxy-phenylamino-1-deoxyribulose phosphate; Ind, Indole-3-glycerol-P; L-Tryp, L-tryptophan.