Switching control of an essential gene for reprogramming of cellular phenotypes in Escherichia coli

Abstract

Biological systems designs require various dynamic controllers capable of modulating cellular phenotypes to adapt to changing environments. Cellular phenotypes are simultaneously affected by combinations of multiple genes that are controlled by global regulators. However, it is difficult to intentionally control the expression of these global regulators dynamically because they are essential for cell survival and are involved in regulatory networks clustered in operons. Here, we designed a platform that allows dynamic modulation of the expression of an essential gene. Using this system, comprising of on/off switches that respond to an extracellular stimulus, we successfully demonstrated the switching control of the expression of fusA encoding elongation factor G (EF-G). An additional control module in this system that responds to changed external signals was shown to provide the capacity to switch gears and reprogram cellular phenotypes with desired timing. Biotechnol. Bioeng. 2012; 109:18751880. (C) 2012 Wiley Periodicals, Inc.