Bioreaction network flux analysis for industrial microorganisms: A review

Calik P. , Ozdamar T.

REVIEWS IN CHEMICAL ENGINEERING, vol.18, no.6, pp.553-596, 2002 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Review
  • Volume: 18 Issue: 6
  • Publication Date: 2002
  • Doi Number: 10.1515/revce.2002.18.6.553
  • Page Numbers: pp.553-596


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.