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Fig. 2 | Microbial Cell Factories

Fig. 2

From: Engineering Escherichia coli for the utilization of ethylene glycol

Fig. 2

Comparison of glycolate bioproduction pathways from substrates of interest. a Glycolate can be bioproduced from a variety of different substrates, including (i) xylose, (ii) glucose and (iii) ethylene glycol (EG). Xylose and glucose are the two most commonly studied substrates; however, glycolate production from these substrates is limited by the interconnectedness of the growth and production pathways, as indicated by their topology and low orthogonality scores. Consequently, efficient production of glycolate from either of these compounds necessitates the coupling of growth and glycolate synthesis. Alternatively, EG assimilation lends itself to a branched topology that permits the decoupling of glycolate synthesis and cell growth (high orthogonality score). b Although Escherichia coli (E. coli) cannot naturally assimilate EG, the conversion of EG to glycolate can be introduced via the overexpression of a mutant propanediol oxidoreductase (encoded by fucO) and glycolaldehyde dehydrogenase (encoded by aldA). The subsequent conversion of glycolate to glyoxylate provides a branch point that serves as a metabolic valve. Under fully aerobic conditions, glycolate is converted to glyoxylate and channeled to the central metabolism for growth via glycerate metabolism. Alternatively, under oxygen limiting conditions glycolate accumulates. Oxygen can thus be used for dynamic control of this metabolic valve, thereby decoupling the production of glycolate and biomass. Colours denote the following: exogenous steps (purple), the desired product (red), biomass precursors (green), and metabolic valves (blue). For production from glucose (A (iii)), red arrows are also used to specify the product pathway. DHAP dihydroxyacetone phosphate, 3PG 3-phosphoglycerate, 2PG 2-phosphoglycerate, PEP phosphoenolpyruvate, AcCoA acetyl-CoA, Cit citrate, Icit isocitrate, Akg alpha-ketoglutarate, SucCoA succinyl-CoA, Succ succinate, Fum fumarate, Mal malate, Oaa oxaloacetate, EG ethylene glycol, TSA tatronate semialdehyde

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