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A mathematical model of kinetics of the biosynthesis of tetracyclines

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Summary

A mathematical model simulating the behaviour or Streptomyces aureofaciens in batch culture under conditions when tetracyclines are synthesized in excessive amounts has been formulated. The response of the mathematical model to the experimental conditions applied corresponds with data obtained in the experiments. The mathematical model demonstrated that the level of tetracycline production is determined during the period of culture growth beginning with exhaustion of inorganic phosphate from the medium and ending with inhibition of the synthesis of enzymes caused by the synthesized tetracyclines. Further tetracycline synthesis is then proportional to the amount of enzymes synthesized in this interval.

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Abbreviations

E :

Activity of ACT-oxygenase (10×nkat/g)

P :

Product concentration (mg/l)

k 1-k 6 :

Rate constants

K S :

Saturation constant (g sugar/l)

K I1 :

Inhibition constant (mg product/l)

K I2 :

Inhibition constant (mM phosphate/l)

K I3 :

Inhibition constant (mg product/l)

S 1 :

Substrate sucrose (g sugar/l)

S 2 :

Substrate concentration — phosphate (mM/l)

r P :

Specific rate of product formation (mg product/g · h)

r E :

Specific rate of enzyme synthesis (10×nkat/g2 · h), Expressed by activity units

t :

Cultivation time (hour)

X :

Biomass dry weight (g/l)

Y S/X :

Yield coefficient

μ:

Specific growth rate (h-1)

References

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  2. Běhal V, Vaněk Z (1970) Regulation of biosynthesis of secondary metabolites. XII. Acetyl CoA carboxylase in S. aureofaciens. Folia Microbiol 15:354–357

  3. BěhalV, PodojilM, HošťálekZ, VaněkZ, LynenF (1974) Regulation of biosynthesis of secondary metabolites. XVI. Origin of terminal group of tetracyclines. Folia Microbiol 19:146–150

  4. Běhal V, Jechová V, Vaněk Z, Hošťálek Z (1977) Alternate pathways of malonyl CoA formation in Streptomyces aureofaciens. Phytochemistry 16:347–350

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Votruba, J., Běhal, V. A mathematical model of kinetics of the biosynthesis of tetracyclines. Appl Microbiol Biotechnol 19, 153–156 (1984). https://doi.org/10.1007/BF00256446

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Keywords

  • Enzyme
  • Inorganic Phosphate
  • Mathematical Model
  • Streptomyces
  • Tetracycline