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Metabolic flux‐based optimisation of recombinant human interleukin‐3 expression by Streptomyces lividans 66
Author(s) -
Nowruzi Keyvan,
Elkamel Ali,
Scharer Jeno M.,
Cossar Douglas,
MooYoung Murray
Publication year - 2011
Publication title -
the canadian journal of chemical engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.404
H-Index - 67
eISSN - 1939-019X
pISSN - 0008-4034
DOI - 10.1002/cjce.20447
Subject(s) - anabolism , fermentation , metabolic flux analysis , metabolism , chemistry , biochemistry , biomass (ecology) , flux (metallurgy) , catabolism , metabolic pathway , amino acid , food science , biology , organic chemistry , ecology
A metabolic reaction network including carbohydrate and amino acid metabolism in both anabolic and catabolic reactions was developed for Streptomyces lividans . Based on observed nutrient consumption, the fermentation process comprised two stages: amino acid uptake in the first phase followed by ammonia uptake as the nitrogen source in the second phase. Linear programming in combination with eight measured input and output fluxes was employed to determine the flux distribution through the major metabolic pathways in both phases of the batch fermentations. Two different objective functions were defined and examined: optimising biomass production by maximising the specific growth rate and optimising a balanced redox metabolism by minimising excess NAD(P)H production. The flux distributions obtained for the two objectives were very similar. The model predicted specific growth rate agreed well (8–10% difference) with observations. A uniform distribution was assumed for each biomass component and the results showed that, using either objective the biomass composition does not have a significant effect on the internal distribution of fluxes.