Design of artificial cell-cell communication using gene and metabolic networks.

@article{citeulike:226, abstract = {Artificial transcriptional networks have been used to achieve novel, nonnative behavior in bacteria. Typically, these artificial circuits are isolated from cellular metabolism and are designed to function without intercellular communication. To attain concerted biological behavior in a population, synchronization through intercellular communication is highly desirable. Here we demonstrate the design and construction of a gene-metabolic circuit that uses a common metabolite to achieve tunable artificial cell-cell communication. This circuit uses a threshold concentration of acetate to induce gene expression by acetate kinase and part of the nitrogen-regulation two-component system. As one application of the cell-cell communication circuit we created an artificial quorum sensor. Engineering of carbon metabolism in Escherichia coli made acetate secretion proportional to cell density and independent of oxygen availability. In these cells the circuit induced gene expression in response to a threshold cell density. This threshold can be tuned effectively by controlling DeltapH over the cell membrane, which determines the partition of acetate between medium and cells. Mutagenesis of the enhancer sequence of the glnAp2 promoter produced variants of the circuit with changed sensitivity demonstrating tunability of the circuit by engineering of its components. The behavior of the circuit shows remarkable predictability based on a mathematical design model.}, address = {Department of Chemical Engineering, University of California, Los Angeles, CA 90095, USA.}, author = {Bulter, T. and Lee, S. G. and Wong, W. W. and Fung, E. and Connor, M. R. and Liao, J. C. }, citeulike-article-id = {226}, doi = {http://dx.doi.org/10.1073/pnas.0306484101}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {genecircuits, metabolic, quorum, sbw\_systemreports, synthetic\_biology}, month = {February}, number = {8}, pages = {2299--2304}, posted-at = {2004-11-12 02:17:30}, title = {Design of artificial cell-cell communication using gene and metabolic networks.}, url = {http://dx.doi.org/10.1073/pnas.0306484101}, volume = {101}, year = {2004} }

TY - JOUR ID - citeulike:226 L3 - citeulike-article-id:226 N2 - Artificial transcriptional networks have been used to achieve novel, nonnative behavior in bacteria. Typically, these artificial circuits are isolated from cellular metabolism and are designed to function without intercellular communication. To attain concerted biological behavior in a population, synchronization through intercellular communication is highly desirable. Here we demonstrate the design and construction of a gene-metabolic circuit that uses a common metabolite to achieve tunable artificial cell-cell communication. This circuit uses a threshold concentration of acetate to induce gene expression by acetate kinase and part of the nitrogen-regulation two-component system. As one application of the cell-cell communication circuit we created an artificial quorum sensor. Engineering of carbon metabolism in Escherichia coli made acetate secretion proportional to cell density and independent of oxygen availability. In these cells the circuit induced gene expression in response to a threshold cell density. This threshold can be tuned effectively by controlling DeltapH over the cell membrane, which determines the partition of acetate between medium and cells. Mutagenesis of the enhancer sequence of the glnAp2 promoter produced variants of the circuit with changed sensitivity demonstrating tunability of the circuit by engineering of its components. The behavior of the circuit shows remarkable predictability based on a mathematical design model. IS - 8 JF - Proc Natl Acad Sci U S A SN - 0027-8424 AD - Department of Chemical Engineering, University of California, Los Angeles, CA 90095, USA. EP - 2304 TI - Design of artificial cell-cell communication using gene and metabolic networks. VL - 101 SP - 2299 KW - genecircuits KW - metabolic KW - quorum KW - sbw_systemreports KW - synthetic_biology AU - Bulter, T AU - Lee, SG AU - Wong, WW AU - Fung, E AU - Connor, MR AU - Liao, JC PY - 2004/02/24/ UR - http://dx.doi.org/10.1073/pnas.0306484101 ER -