Model Approach for Biotechnology and Bioengineering

To what extent is industrial biotechnological process optimally designed? Do the biological entities (enzymes, cells) involved in the biotechnological process operate efficiently? What could be done to improve the efficacy? Answers to the questions are often not quite simple. Primarily, it is dictated by large-scale and expensive experimental investigations characterizing phenomenon from various positions. However, it is only one side of the problem because results of these investigations should be integrated in the sole description and correctly interpreted to address the questions posed.

The first part of the problem does not usually cause any complications, because lots of experimental information characterizing different biotechnological subjects (strains, enzymes or fermenters) has been collected and published. However, the other part of the problem consisting of integration and interpretation of the data could have serious troubles. For address the issue we propose to apply methods of computational systems biology to analyze  biotechnological experimental data.

Model approach allows us to solve such problems as:

By this day we have developed mathematical models of the most biotechnologically important objects in our Institute. So, we have models of metabolic pathways and systems of:



Example 1 - Strain Improvement

 

thumb_strain_improve2.jpgIn the framework of collaboration with GlaxoSmithKline a 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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Example 2 - Increase of Biotechnology Production Effectivenes

thumb_pacs_0.jpg Industrial production of drugs and/or their components is based very often on the work of an enzyme which catalyses the reaction of their synthesis. Drug production in the industrial quantities with the assistance of enzymes requires often the optimization of process in the reactor. Indeed on the several steps of production cycle several by-products, which pollute final product and increase its yield might be produced concurrently with the main product. Furthermore enzyme which catalyzes the reaction of product formation may be inactivated or works nonoptimally in the conditions of industrial production. Thus, the competent control of process which takes place in the reactor on the every step of technological cycle is required for increase of production effectiveness. It may be fulfilled by using of special program product which should answer at least two main requirements  - take into consideration all the features of industrial process and account in detail the mechanism of enzyme action. The method developed takes all these factors into account.

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