Metabolic network analysis for human therapeutic protein productions: Effects of the P/O ratio

Calik P., Ozdamar T.

Conference of the Microbial Physiology Section of the European-Federation-of-Biotechnology, SEMMERING, Austria, 5 - 08 October 2000, pp.277-288 identifier

  • Publication Type: Conference Paper / Full Text
  • Country: Austria
  • Page Numbers: pp.277-288


The metabolic fluxes through the central carbon pathways in the bioprocesses for human leukocyte interferon (IFN-alpha(1)) and erythropoietin (EPO) overproductions by recombinant Bacillus sp, carrying the related human genes were determined separately, on two alternative carbon sources, i.e. glucose and citrate, which have different reduction degrees. In addition, the influence of the P/O ratio on the cell growth, IFN-alpha(1) and EPO productions were investigated. Thus, the potential influence of increased energy coupling in oxidative phosphorylation is also presented. In parallel to the increase in P/O ratio, with each substrate tested, cell growth and total ATP generation rates increased significantly. The interactions between specific cell growth and protein synthesis rates in the transition periods were analysed for the production of IFN-alpha(1) and EPO. The influence of the P/O ratio on metabolic flux distributions was significant at high specific growth rates; further, with the decrease in the growth rate in the transition period, the IFN-alpha(1) and EPO synthesis fluxes increased. During the product synthesis period (mu = 0 h(-1)) for both substrate, the P/O ratio influences neither the EPO synthesis nor the IFN-alpha(1) synthesis significantly. The potential strategies for improving IFN-alpha(1) and EPO productions are discussed.