Example 1 - Strain Improvement

Problem: to increase productivity of Escherichia coli industrial strain designed for high production of thymidine.

Subject of inquiry: E. coli industrial strains.

Approach:
  • To develop and verify kinetic model of pyrimidine biosynthesis pathway in E. coli cells.
  • Based on analysis of the model behavior to propose mutation program for strain improvement modifications.
strain_improve1.jpg Result №1: Model of E. coli pyrimidine biosynthesis pathways has been developed.
Result №2: This model has been verified against different types of experimental data.
strain_improve2.jpg
Result №3: Based on the analysis of the model behavior we have proposed program of genetic modifications and changes in culture conditions which are necessary for strain improvement.
 
Result №4: Practical realization of this program has increased the yield of thymidine in the industrial scale on 23%.

Conclusions

А program of gene modifications of Escherichia coli strain which produces one of the components of azidothymidine has been developed. Kinetic model of pyrimidine biosynthesis has been developed and verified against experimental data and 9 predictions has been suggested indicating what and how gene modifications should be implemented in existing industrial strain. Practical realization of this program has increased the yield of this medical component on an industrial scale on 23%.

 

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