Difference between revisions of "Directed Evolution and Synthetic Biology - Hunter Stone"
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My project will focus on attempts to utilize random mutations for optimization of synthetic pathways. Mathematical modeling of synthetic pathways is a powerful, proven tool to maximize product output. However, authors have recently shown that recombinant methods can be used to discover previously unknown elements of cell metabolism that will increase product yield even further. These methods of directed evolution have also been used to create powerful tools like promoters of specific expression levels, further increasing the relevance and importance of these methods to synthetic biology. | My project will focus on attempts to utilize random mutations for optimization of synthetic pathways. Mathematical modeling of synthetic pathways is a powerful, proven tool to maximize product output. However, authors have recently shown that recombinant methods can be used to discover previously unknown elements of cell metabolism that will increase product yield even further. These methods of directed evolution have also been used to create powerful tools like promoters of specific expression levels, further increasing the relevance and importance of these methods to synthetic biology. | ||
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| + | Researcher Jay Keasling has recently described a genetically-modified yeast strain that produces artemisinic acid, a chemical precursor to the antimalarial drug artemisinin. In these experiments, his team engineered yeast cells to express enzymes in a pathway that converts farnesyl pyrophosphate (FPP), a metabolic intermediate naturally occurring in yeast, into the desired product. However, in order to make this pathway generate a desirable amount of product, his team also had to tweak the existing yeast metabolism to ensure enough FPP was produced to channel through the synthetic pathway. In these manipulations, Keasling’s team was addressing a problem that faces many projects in synthetic biology, especially those aimed at producing a specific product: pathway optimization. Although we are increasingly able to build sophisticated constructs within living cells, the existence of these frameworks does not always correspond with their ability to fulfill their intended purposes efficiently and effectively. | ||
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| + | To maximize the amount of FPP produced, Keasling’s team increased the expression levels of the enzymes in the mevalonte pathway (Fig. 1). He also directed FPP away from the sterol biosynthetic pathway by repressing the enzyme responsible for conversion of FPP to squalene (Fig. 1). Although their methods were effective in producing desired products, the optimization of this biosynthetic pathway was limited only to augmenting the expression levels to only the known elements in the mevalonate pathway. Indeed, the researchers indicated that the yeast strain they developed requires furthers optimization to make the drug production system more commercially feasible. What other changes to the yeast strain could enhance product formation? Were the expression levels the researchers chose truly the best for meeting their goals? Could additional changes to other pathways or protein-protein interactions have lead to increases in product formation or decreases in product consumption? Could the enzymes themselves be more efficient in their catalytic activities? | ||
Revision as of 06:52, 13 November 2007
Project Proposal
My project will focus on attempts to utilize random mutations for optimization of synthetic pathways. Mathematical modeling of synthetic pathways is a powerful, proven tool to maximize product output. However, authors have recently shown that recombinant methods can be used to discover previously unknown elements of cell metabolism that will increase product yield even further. These methods of directed evolution have also been used to create powerful tools like promoters of specific expression levels, further increasing the relevance and importance of these methods to synthetic biology.
Researcher Jay Keasling has recently described a genetically-modified yeast strain that produces artemisinic acid, a chemical precursor to the antimalarial drug artemisinin. In these experiments, his team engineered yeast cells to express enzymes in a pathway that converts farnesyl pyrophosphate (FPP), a metabolic intermediate naturally occurring in yeast, into the desired product. However, in order to make this pathway generate a desirable amount of product, his team also had to tweak the existing yeast metabolism to ensure enough FPP was produced to channel through the synthetic pathway. In these manipulations, Keasling’s team was addressing a problem that faces many projects in synthetic biology, especially those aimed at producing a specific product: pathway optimization. Although we are increasingly able to build sophisticated constructs within living cells, the existence of these frameworks does not always correspond with their ability to fulfill their intended purposes efficiently and effectively.
To maximize the amount of FPP produced, Keasling’s team increased the expression levels of the enzymes in the mevalonte pathway (Fig. 1). He also directed FPP away from the sterol biosynthetic pathway by repressing the enzyme responsible for conversion of FPP to squalene (Fig. 1). Although their methods were effective in producing desired products, the optimization of this biosynthetic pathway was limited only to augmenting the expression levels to only the known elements in the mevalonate pathway. Indeed, the researchers indicated that the yeast strain they developed requires furthers optimization to make the drug production system more commercially feasible. What other changes to the yeast strain could enhance product formation? Were the expression levels the researchers chose truly the best for meeting their goals? Could additional changes to other pathways or protein-protein interactions have lead to increases in product formation or decreases in product consumption? Could the enzymes themselves be more efficient in their catalytic activities?
