Keasling Lab

Synthetic Biology

Synthetic biology is the design and construction of biological systems–generally from basic components — to solve important problems or to better understand a biological phenomenon.  The Keasling Lab has focused on the development of basic synthetic biology tools to make it easier to design, construct and control metabolism inside cells.  These tools include programmable genetic control elements, DNA design and assembly methods, and engineered enzymes to synthesize unnatural chemicals.

Programmable genetic control systems

For many applications of synthetic biology and metabolic engineering, accurate control over protein production is essential. Over-expression of genes encoding enzymes in a metabolic pathway can cause significant burden on cells, whereas low expression can create bottlenecks, or accumulation of toxic metabolic intermediates. Hence, precise expression of genes encoding the metabolic pathway enzymes is crucial for high production of desired products. The Keasling Lab has engineered a variety of genetic control systems (synthetic promoters, protein tags and scaffolds, and biosensors) that enable precise control of gene expression for these purposes. Example publications include:

DNA design & assembly

Synthetic biology today differs from more traditional genetic engineering in that it employs more powerful tools to design and construct biological systems.  The Keasling Lab has been involved in developing tools and methodologies to facilitate synthetic biology.  These include Computer-Aided Design software, CRISPR/Cas9-based DNA assembly schemes, and novel DNA synthesis methods. Example publications include:

Engineering novel enzymes

Many metabolic engineering applications require a combination of natural enzymes and ones engineered to catalyze a particular reaction or when the native enzyme is somehow insufficient. The Keasling Lab has engineered isoprenoid cyclases to have new or more focused activities, complexes of scaffolded enzymes to increase flux through metabolic pathways, and polyketide synthases to produce unnatural chemicals. The enzymes attached to the protein scaffold is an example where we learned how nature scaffolds enzymes and constructed a scaffolding system for application to metabolic pathways. The polyketide synthases are nature’s best examples of scaffolded enzymes.  Example publications include:

Y. Yoshikuni, T. E. Ferrin, and J. D. Keasling. 2006. Designed divergent evolution of enzyme function.  Nature  

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