Synthetic Biology


The term “synthetic biology” was first used 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 is often more of 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.

In chemistry, this new area of research has the 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 of this research are asking whether chemists can design new molecules and pathways that can successfully function in biochemical and biological systems. Some of these molecules are intended to function in existing living systems, while others may one day be part of altogether new, human-designed living systems.

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

Examples of synthetic biology research in the Kool lab include:

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

• Design of new DNA-like, helical paired genetic systems (xDNA project). xDNA has been successfully used to encode bacterial phenotype (J. Am. Chem. Soc., 2011, ASAP.) and can be successfully incorporated by DNA polymerases (Org. Biomol. Chem., 2010, 8, 2704-2710.).

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.

For information on the engineering side of synthetic biology research, see: Synthetic