"
Team:Wageningen UR/Flux balance analysis
From 2013.igem.org
Karrenbelt (Talk | contribs) |
Karrenbelt (Talk | contribs) |
||
| Line 21: | Line 21: | ||
<h2> Rationale </h2> | <h2> Rationale </h2> | ||
<p> | <p> | ||
| - | + | Producing a compound in a novel host at first requires investigation of the possibility to do so. Since the compounds required for biosynthesis of lovastatin are occur naturally in metabolic routes such as the citric acid cycles and fatty acid synthesis pathways, all of the Aspergilli that are modeled have the potential ability to produce lovastatin when the required genes are introduced. Analysis and comparison of the different models allows for a broad insight in efficient biosynthesis strategies. | |
</p> | </p> | ||
Revision as of 13:43, 15 September 2013
- Safety introduction
- General safety
- Fungi-related safety
- Biosafety Regulation
- Safety Improvement Suggestions
- Safety of the Application
Metabolic modeling
Metabolic modeling
of lovastatin biosynthesis in Aspergilli
Introduction
To develop and investigate mathematical models of metabolic processes is one of the primary challenges in systems biology. As a proof of concept of our modular domain approach lovastatin has been chosen and its production in several Aspergilli will be modeled. To investigate the potential of lovastatin production in A. niger, A. nidulans, A. oryzae will be compared to that in A. terreus.
Rationale
Producing a compound in a novel host at first requires investigation of the possibility to do so. Since the compounds required for biosynthesis of lovastatin are occur naturally in metabolic routes such as the citric acid cycles and fatty acid synthesis pathways, all of the Aspergilli that are modeled have the potential ability to produce lovastatin when the required genes are introduced. Analysis and comparison of the different models allows for a broad insight in efficient biosynthesis strategies.
Aim
• Model and balance the lovastatin pathway
• Expand the metabolic model of A. niger, A nidulans, A. oryzae with the lovastatin biosynthesis pathway
• Perform flux balance analysis to analyze the flux of lovastatin and compare this with the model of A. terreus
• Flux variability analysis to determine the ranges of fluxes that correspond to an optimal solution determined through flux balance analysis
• Change media composition in the model to investigate its effect on lovastatin production
• Use OptKnock to determine gene deletion strategies leading to increased production of lovastatin
Approach
Research Methods
The COBRA toolbox facilitates easy input of the metabolic model in SBML to perform these calculations in MATLAB. Once the model has been expanded flux balance analysis allows for a genome-scale approach. OptKnock can be used to determine which gene knockouts should increase the metabolic flux towards lovastatin.
