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Analysis of metabolic fluxes for hyaluronic acid (HA) production by Streptococcus zooepidemicus


A detailed metabolic flux analysis (MFA) for hyaluronic acid (HA) production by Streptococcus zooepidemicus was carried out. A metabolic network was constructed for the metabolism of S. zooepidemicus. Fluxes through these reactions were estimated by MFA using accumulation rates of biomass and product, consumption rate of glucose in batch fermentation and dissolved oxygen-controlled fermentation. The changes of the fluxes were observed at different stages of batch fermentation and in different dissolved oxygen tension (DOT)-controlled fermentation processes. The effects of metabolic nodes on HA accumulation under various culture conditions were investigated. The results showed that high concentration of glucose in the medium did not affect metabolic flux distribution, but did influence the uptake rate of glucose. HA synthesis was influenced by DOT via flux redistribution in the principal node. Adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH) produced in the fermentation process are associated with cell growth and HA synthesis.

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I :

Identification matrix of reaction equation

R :

Reactant matrix

R' :

Matrix of reaction equation matrix

x e :

Accumulation rate of extracellular substance (mol/L/h)

r :

Net transformation rate of reactants (mol/L/h)

S :


ν :


ψ :

Measurement noise variance-covariance matrix associated with x

R :

Rank of matrix

x i :

Accumulation rate of intracellular substance (mol/L/h)

x :

Matrix of net transformation rate

S :

Matrix of stoichiometric coefficient


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Correspondence to Hai-Jun Gao.




Table 1 Appendix A. Metabolic reactions in Streptococcus zooepidemicus.


Table 2 Appendix B. Metabolic accumulation rate vector and abbreviations used in metabolic reactions.

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Gao, H., Du, G. & Chen, J. Analysis of metabolic fluxes for hyaluronic acid (HA) production by Streptococcus zooepidemicus . World J Microbiol Biotechnol 22, 399–408 (2006). https://doi.org/10.1007/s11274-005-9047-7

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  • dissolved oxygen tension (DOT)
  • fermentation
  • hyaluronic acid
  • metabolic flux analysis (MFA)
  • Streptococcus zooepidemicus