Bioreaction network flux analysis for human protein producing Bacillus subtilis based on genome-scale model

To interpret the effect of human protein gene, e.g., human growth hormone gene hGH, on the intracellular bioreaction network of Bacillus subtilis, the intracellular reaction fluxes were calculated by solving the mass-balance-based genome-scale mathematical model, at pseudo-steady state by using bioreactor data. The bioreaction network consists of 1340 reactions including 990 metabolites. Reaction fluxes in B. subtilis carrying pMK4::pre(subC)::hGH (rBsHGH) and B. subtilis carrying merely pMK4 (rBsP) were calculated to identify the existence of pathways and to elucidate the physiological state of the cells. Considering the characteristic cell and recombinant hGH (rhGH) concentration profiles of rBsHGH, the bioprocess was divided into five periods. The reaction network of rBsHGH started operation with 328 reactions (Period I: 0