Teaching bacteria a new language

In the nascent field of synthetic biology (1), the engineering of novel cell–cell communication capabilities will become critical. Synthetic biology involves the creation of artificial gene and metabolic networks to program new cell and organism behaviors. Recent accomplishments have demonstrated that cells can be engineered to carry out novel tasks (refs. 2–10; R.W. and S. Basu, www.hpcaconf.org/hpca8), and hint that someday we will be able to program cell behaviors with the same ease and capability that we now program computers. However, to achieve higher level functions, we need to program individual cells to coordinate their activities. Previous efforts achieved such coordination by taking existing quorum sensing (QS) components from a source host, Vibrio fischeri, and integrating them into a target host, Escherichia coli (5, 7, 8). The work of Bulter et al. (11) in this issue of PNAS describes a new form of engineering cell–cell communication based on manipulating metabolic pathways. Specifically, the authors engineered the nitrogen regulation system and the acetate pathway in E. coli. As the engineered cells grow, they broadcast their presence by producing and secreting acetate. This intercellular signal is then detected by neighboring cells that respond by elevating the expression of a GFP. Because the acetate level correlates with cell density, this process confers QS behavior on the cells without using traditional QS biochemistry.

Fig. 1 shows the circuit operation. First, during normal cell metabolism, amino acid biosynthesis results in acetate as a byproduct. Acetate, which functions as the communication signal, is readily converted between several forms in the cells. The protonated form of acetate, acetic acid, diffuses out of the cell to the growth media and then into neighboring cells. When in the cytoplasm, …