Bioreaction network flux analysis for industrial microorganisms: A review

This review focuses on the analysis of the bioreaction networks of the microorgansims used in fermentation processes, by metabolic flux analysis that is the novel tool of biochemical reaction engineering, required for the quantitative analysis of cell metabolism which is under the control of the cell physiology. Metabolic flux analysis (MFA) is based on calculation of intracellular reaction network rates through various reaction pathways either theoretical or by using elaborate experimental data on uptake, excretion, secretion rates, biosynthetic requirements with metabolic stoichiometry - by solving the mass-balance-based mathematical model developed for the bioreaction network components, either at pseudo-steady state or at steady-state. MFA describes the interactions between the cell and the bioreactor with proper emphasis on the metabolic state and the metabolic process in order to fine-tune the bioreactor performance. This analysis can be used to find the critical branch points and bottlenecks in the overall flux distributions, for modifying the medium composition, for improving the bioreactor operation conditions, moreover for calculating the theoretical metabolic capacities of the microorganism, and for selecting the host microorganism. The methodology of the metabolic flux analysis is provided briefly; thereafter, a comprehensive overview of the state-of-the-art pertaining to cell growth and synthesis of biomolecules in the organisms, i.e. Candida lipolytica, Propionibacterium, Candida utilis, Escherichia coli, Corynebacterium glutamicum, Corynebacterium melassecola, Brevibacterium flavum, Penicillium chrysogenum, Saccharomyces cerevisiae, Streptomyces lividans, Aspergilus niger, Aspergilus oryzae, Bacillus subtilis, Bacillus licheniformis, Ashbya gossypii, Lactococcus lactis, Clostridium acetobutylicum, Torulopsis glabrata, Zymomonas mobilis, Haemophilus influenzae, Streptomyces coelicolor, hybridoma cells, baby hamster kidney cells, Chinese hamster ovary cells, and human liver cells, are given in order to understand the cellular metabolism and the physiology to improve the cellular activities of the cells.


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In this study, a methodology for separation of chiral molecules, by using enhanced ultrafiltration system was developed. Benzoin was the model chiral molecule studied. In the scope of developing this methodology, some parameters were investigated in the preliminary ultrafiltration experiments in order to set the operation conditions for enhanced ultrafiltration experiments. Due to the slight solubility of benzoin in pure water, 15% (v/v) Polyethylene glycol (PEG 400) and 30 % (v/v) Dimethyl sulfoxide (DMSO)...
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In this study, supercritical carbon dioxide (scCO(2)) deposition was used to prepare vulcan-supported Pt (Pt/Vulcan) electrocatalysts for proton exchange membrane fuel cells (PEMFCs), and the effects of process variables on the properties of the electrocatalysts were investigated. The two different methods used to reduce the organometallic precursor were thermal reduction in nitrogen at atmospheric pressure and thermal reduction in scCO(2). In the former method, the maximum Pt loading achieved was 9%, and t...
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Bioreaction network flux analysis for human protein producing Bacillus subtilis based on genome-scale model
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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 ca...
Citation Formats
P. Çalık, “Bioreaction network flux analysis for industrial microorganisms: A review,” REVIEWS IN CHEMICAL ENGINEERING, pp. 553–596, 2002, Accessed: 00, 2020. [Online]. Available: