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Synthetic Biology

The term "synthetic biology" was introduced long ago by the molecular biologist W. Szybalski. Molecular biologists and engineers are very interested in assembling and engineering new genetic pathways for altering the phenotypes of living cellular systems. This has been called a "top-down" approach to cellular design.


The chemical approach to synthetic biology often involves a "bottom-up" strategy, in which the basic molecules of life (nucleic acids, amino acids, carbohydrates) are redesigned and then inserted back into living systems (see article by R. Rawls entitled "'Synthetic Biology' Makes Its Debut" in Chemical & Engineering News, April 24, 2000, p. 49-53). Both approaches are making important contributions to science and technology.


In chemistry, this emerging area of research has a main aim of developing new molecular components of biological pathways and organisms. It is a natural offshoot of the older field termed "biomimetic chemistry", and it reflects the rapidly increasing sophistication of knowledge and methodology in the fields of biochemistry, biophysics, molecular biology, and organic chemistry. Molecular design and synthesis are two critical components of chemical synthetic biology. Practitioners are designing new molecules and pathways that can successfully function in biochemical and biological systems, in order to probe and/or alter them.


Progress in synthetic biology research will lead to increased knowledge of natural biomolecules and pathways, and will also yield useful new technologies for studying nature and diagnosing and treating human disease.


Examples of chemical synthetic biology research in the Kool lab include:


• Design of new DNA bases that function accurately and efficiently in natural DNA replication pathways. This has led to the first example of a nonnatural DNA base that functions correctly in a living cell (e.g., Proc. Natl. Acad. Sci. USA 2005, 102, 15803-15808)

• Design of new DNA-like, helical paired genetic systems that can encode information in living cells (xDNA project) (e.g., J. Am. Chem. Soc. 2011, 133, 18447-18451)

• Development of a size-expanded RNA genetic set that is fluorescent and functions in siRNAs in living cells. (e.g. ACS Chem. Biol. 2012, 7, 1454-1461)

For additional discussion of synthetic biology, see: S. A. Benner, Nature 2003, 421, 118 and E. T. Kool and M. L. Waters, Nature Chem. Biol. 2007, 2, 70-73.