CHE.496/2008/Responses/a12

Metabolic pathway engineering

• Discussion leader: Patrick Gildea (Discussion guide)

Eyad Lababidi's Response

• Bioengineering novel in vitro metabolic pathways using synthetic biology
  • Okay so i read this article but i constantly had to reread sections because i was missing the point. I believe it was about how to create new enzymes in cells and the article discussed the most effective way to model the enzymes, but i really wasn't sure how it was relevant to us or how the methods they were using were relevant to us, so the article seemed a bit dense to me and to be honest i didnt really get much out of it, sorry George.
• Synthetic biology for synthetic chemistry
  • This articles is a very good all encompassing crash course to how one would start a Igem project. Each important piece of a synthetic bio cell is defined and explained to best be setup for a cell meant to be harnessed for synthetic biology. The insight on factors that could destroy a project especially through differing metabolic rates seems useful. other explanations were also useful such as why synth bio parts have been mutated to be a bare bones chassis that will readily take up plasmid vectors and evolutionary abilities of the cell have been disabled such as to not evolve away from containing the plasmid.

Eyad Lababidi 01:25, 10 March 2008 (EDT)

Kevin Hershey's Response

• Bioengineering novel in vitro metabolic pathways using synthetic biology
  • The article by Meyer et. al. discusses modeling in synthetic biology. The article begins by discussing multi-enzyme assembly, which can in itself present many challenges. Then, it discusses data generation from these enzymes. The generation can be troublesome because it needs to be obtained on the small scale in vitro experiments. Once the data is compiled, mathematical models are fit to the data. These are mostly differential equations dealing with mass balances and rate constants. With the system modeled, the network can then optimized due to the engineering principles of synthetic biology.
• Synthetic biology for synthetic chemistry
  • The review by Keasling discusses some of the new principles and applications to synthetic biology. It begins by discussing the ideal chassis. This chassis would be very robust, hardy, and capable of surviving on minimal carbon. Information on the chassis is insightful from this author, who produced the minimal genome organism. He then discusses artemisinin, an anti-malarial drug, production. The advantage to this synthetic biology approach is that the precursor to artemisinin is squalene. Squalene is used as many other precursors, and the modular approach will allow Keasling and team to produce valuable products based on their work so far.
• KPHershey 15:15, 12 March 2008 (CDT)

George Washington's Response

• Bioengineering novel in vitro metabolic pathways using synthetic biology
  • This article discussed the techniques available today for development of entire metabolic pathways for use in industrial production of biological chemicals. It seemed to focus heavily on the analysis of experimental data, as there are ways to start with a (usually non-linear) model, extract parameters for the model from experimental data through various mathematical techniques, and even use those data to suggest ways to improve the model or what parameters need to be enhanced. Thus, straightforward experimentation can pinpoint which enzymes need to be modified, and how. Modifying the proteins can be extremely difficult, although often possible. While all this sounds great, it still feels extremely computationally and conceptually intensive, so truly optimizing a many enzyme system may prove outside of our ability. However, if optimization is not as important, we could probably develop a system with a reasonable model, although we would not be able to ensure our model is completely accurate without much work. The iterative approach described in the article should suffice to permit enzymes to be made and tested one at a time, only having to do fine-tuning when there is inhibition back in the chain.
• George Washington 16:53, 12 March 2008 (CDT)