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Fig. 5 | BMC Systems Biology

Fig. 5

From: Optimization of lipid production with a genome-scale model of Yarrowia lipolytica

Fig. 5

Acetyl-CoA and NADPH – yields and balances. a: comparison of simulations with different sources for NADPH. In the unconstrained network, NADPH is generated in the PPP, resulting in the highest lipid yield. For Idh, Mae and the mannitol cycle (Man) the yield drops to ca. 90 % of the yield obtained with active PPP. If NADPH is generated by succinate semialdehyde dehydrogenase (Suc) or tetrahydrofolate synthase (Thf) the lipid yield is reduced to ca. 48 % and 61 %, respectively. b: the graph shows the ratios of mmol acetyl-CoA and NADPH produced per mmol of glucose consumed. The colors indicate the ratios required for lipid accumulation (violet) and other processes (brown). The actual rates (in mmol g−1 h−1) are shown as numbers. Availability of acetyl-CoA as the carbon substrate and NADPH as the reductive power are regarded as the two most important factors for FA synthesis but FBA shows that the rates of acetyl-CoA and NADPH synthesis drop significantly when the cells switch to lipogenesis, from 4.251 to 0.176 mmol g−1 h−1 and from 2.757 to 0.322 mmol g−1 h−1, respectively. This might suggest that overexpression of these pathways is not necessary for higher lipid content. However, the flux distribution at the glucose-6-phosphate node changes dramatically, with all glucose directed towards the PPP to provide sufficient NADPH during lipid synthesis. Since only ca. 35 % of glucose-6-phosphate enter the PPP during growth, a regulatory mechanism is required that redirects all glucose towards this pathway in lipogenesis (see Discussion)

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