System-level analysis of tryptophan regulation in Escherichia coli – performance under starved and well-fed conditions

Abstract

Biological systems respond appropriately to a variety of environments thus representing complex systems with rich physiological behavior. Quantitative models can be used to identify the design components that result in the system complexity. In this work, the tryptophan system of Escherichia coli that synthesizes tryptophan internally when faced with starvation in a rapid manner and shuts off the synthesis sluggishly when the cells are exposed to a medium replete with tryptophan has been discussed. The evolved regulatory design is capable of providing such an asymmetric response that represents an appropriate behavior to ensure survival. The tryptophan system uses three distinct regulatory mechanisms namely genetic regulation, transcriptional attenuation and enzyme inhibition to achieve its goals. It has been shown that genetic repression and attenuation are the only active regulatory mechanisms during moderate and severe starvation. However, as the degree of starvation increases, repression is relieved prior to attenuation. The analysis also shows that enzyme inhibition does not play a role under severe starvation and plays a marginal role in increasing the rate of repression when the cells are exposed to well-fed conditions. Finally, we use tools from linear systems theory to rationalize the above observations based on the poles and zeros of an approximated linear system.