Team:NAU-CHINA/Model

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  • Proof of Concept
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  • Model
  • Notebook
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Introduction

Human have had a deep insight in bacterium,and have known more than ever before about how to take good advantage of them. As bacterium feature in fast growth,recipe wide,convenient to modify genes,we can make adjustment to them,when the wild type can’t fit us well, and employ the mutants to do some production or degradation. Normally mutants may be more efficient than wild type,but a problem have confused many people is degeneration. A reason cause degeneration may be the strain which can meet a certain requirement in factory,do not suit the fermentation environment best better than other mutants,that is, there may be some mutants in the stain growth batter,but lost the function we expected. Once their amount become more than the engineering bacteria,the strain will exhibit degeneration.

So degeneration can be influenced by natural selection. How to reduce the pressure of the environment?We have the idea that the expression of non-essential protein and the metabolic structure will influence metabolic rate and genetic stability.

To varify the idea, In our model we focused on quantitative analysis of the pathway involved in the degradation metabolism of 3-pba in E.coli.This type of analysis of cellular metabolism can be used to gain a better understanding of the adding pathway’s influence in E.coli and identify key targets for genetic manipulation that could enhance the degradation pathway.

Left is the main metabolic network in E.coli while right is the engineering E.coli in our project. And the extra part is show by red. Which can help to utilize the 3-pba.

Studies show that the metabolism shows rigidity in bacteria[1],[2]. That is the central metabolic network including PYR won’t change a lot when 3-pba entering into the metabolic network. So in our work we didn’t take care of the concentration of PYR.

In our work,we will discuss the modeling in three aspects：dynamic model,benefits and cost analysis and metabolic control analysis(MCA).

The development of a dynamic model can help us learn the dynamic change within the cell and the control structure. By benefits and cost analysis,we can know the metabolic burden of producing these extra proteins while by MCA we can learn the control structure of the metabolic network so as to do an efficient adjustment. With the adjustment, the network is expected to reach a faster degradation rate within a certain metabolic burden.

Assumption: regulate the expression of non-essential protein and the metabolic structure will gain a fast metabolic rate and better genetic stability.

1. Dynamic model ->Click to see more
2. Metabolic control analysis ->Click to see more
3. Benefits and cost analysis ->Click to see more

Reference

1. Fischer, E. and U. Sauer, Large-scale in vivo flux analysis shows rigidity and suboptimal performance of Bacillus subtilis metabolism. Nat Genet, 2005. 37(6): p. 636-40.
2. Angela Cintolesi, J.M.C., 1 Venetia Rigou,1 Kyriacos Zygourakis,1,2 and Ramon Gonzalez1, < Quantitative Analysis of the Fermentative Metabolism of Glycerol in Escherichia coli >. 3 June 2011.