Cytosolic NADPH balancing in Penicillium chrysogenum cultivated on mixtures of glucose and ethanol

Cytosolic NADPH balancing in Penicillium chrysogenum cultivated on mixtures of glucose and ethanol

Zhao, Z.
Kuijvenhoven, K.
Van Gulik, W.M.
Heijnen, J.J.
Van Winden, W.A.
Verheijen, P.J.T.

Applied Sciences

Biotechnology

2010-08-31

The in vivo flux through the oxidative branch of the pentose phosphate pathway (oxPPP) in Penicillium chrysogenum was determined during growth in glucose/ethanol carbon-limited chemostat cultures, at the same growth rate. Non-stationary 13C flux analysis was used to measure the oxPPP flux. A nearly constant oxPPP flux was found for all glucose/ethanol ratios studied. This indicates that the cytosolic NADPH supply is independent of the amount of assimilated ethanol. The cofactor assignment in the model of van Gulik et al. (Biotechnol Bioeng 68(6):602–618, 2000) was supported using the published genome annotation of P. chrysogenum.Metabolic flux analysis showed that NADPH requirements in the cytosol remain nearly the same in these experiments due to constant biomass growth. Based on the cytosolic NADPH balance, it is known that the cytosolic aldehyde dehydrogenase in P. chrysogenum is NAD+ dependent. Metabolic modeling shows that changing the NAD+-aldehyde dehydrogenase to NADP+-aldehyde dehydrogenase can increase the penicillin yield on substrate.

isotopic non-stationary 13C flux analysis
metabolic flux ratio analysis
pentose phosphate pathway
metabolic engineering
NADPH metabolism

http://resolver.tudelft.nl/uuid:e7d22779-a326-4b44-898d-38ed6799a5e7

https://doi.org/10.1007/s00253-010-2851-5

Springer

0175-7598

Applied Microbiology and Biotechnology, 89 (1), 2011

Institutional Repository

journal article

(c) 2010 The Author(s)