Dynamic model of Escherichia coli tryptophan operon shows an optimal structural design.

A mathematical model has been developed to study the effect of external tryptophan on the trp operon. The model accounts for the effect of feedback repression by tryptophan through the Hill equation. We demonstrate that the trp operon maintains an intracellular steady-state concentration in a fivefold range irrespective of extracellular conditions. Dynamic behavior of the trp operon corresponding to varying levels of extracellular tryptophan illustrates the adaptive nature of regulation. Depending on the external tryptophan level in the medium, the transient response ranges from a rapid and underdamped to a sluggish and highly overdamped response. To test model fidelity, simulation results are compared with experimental data available in the literature. We further demonstrate the significance of the biological structure of the operon on the overall performance. Our analysis suggests that the tryptophan operon has evolved to a truly optimal design.

[1]  Catherine L. Lawson,et al.  The three-dimensional structure of trp repressor , 1985, Nature.

[2]  M. Giona,et al.  Modified model for the regulation of the tryptophan operon in Escherichia coli. , 2002, Biotechnology and bioengineering.

[3]  Mark Ptashne,et al.  λ Repressor and cro—components of an efficient molecular switch , 1981, Nature.

[4]  S. Sinha Theoretical study of tryptophan operon: Application in microbial technology , 1988, Biotechnology and bioengineering.

[5]  J E Bailey,et al.  Genetically structured models forlac promoter–operator function in the Escherichia coli chromosome and in multicopy plasmids: Lac operator function , 1984, Biotechnology and bioengineering.

[6]  A. K. Sen,et al.  Dynamic analysis of genetic control and regulation of amino acid synthesis: The tryptophan operon in Escherichia coli , 1990, Biotechnology and bioengineering.

[7]  A. Joachimiak,et al.  The structural basis for the interaction between L-tryptophan and the Escherichia coli trp aporepressor. , 1987, The Journal of biological chemistry.

[8]  D. Koshland,et al.  Amplification and adaptation in regulatory and sensory systems. , 1982, Science.

[9]  M C Mackey,et al.  Dynamic regulation of the tryptophan operon: a modeling study and comparison with experimental data. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C. Yanofsky,et al.  Physiological studies of tryptophan transport and tryptophanase operon induction in Escherichia coli , 1991, Journal of bacteriology.

[11]  B. Goodwin Oscillatory behavior in enzymatic control processes. , 1965, Advances in enzyme regulation.

[12]  Babatunde A. Ogunnaike,et al.  Process Dynamics, Modeling, and Control , 1994 .

[13]  B. T. Koh,et al.  A Simple genetically structured model of trp repressor–operator interactions , 1993, Biotechnology and bioengineering.

[14]  C. Yanofsky,et al.  Repression is relieved before attenuation in the trp operon of Escherichia coli as tryptophan starvation becomes increasingly severe , 1984, Journal of bacteriology.

[15]  P. J. Bhat,et al.  Quantitative Model for Gal4p‐Mediated Expression of the Galactose/Melibiose Regulon in Saccharomyces cerevisiae , 1999, Biotechnology progress.

[16]  An-Ping Zeng,et al.  Nonlinear Dynamics of Regulation of Bacterial trpOperon: Model Analysis of Integrated Effects of Repression, Feedback Inhibition, and Attenuation , 2002, Biotechnology progress.

[17]  D. Zipser,et al.  The lactose operon , 1970 .

[18]  C. Yanofsky,et al.  Role of regulatory features of the trp operon of Escherichia coli in mediating a response to a nutritional shift , 1994, Journal of bacteriology.

[19]  J. G. Ziegler,et al.  Optimum Settings for Automatic Controllers , 1942, Journal of Fluids Engineering.

[20]  R. Gunsalus,et al.  Interaction of the Escherichia coli trp aporepressor with its ligand, L-tryptophan. , 1986, The Journal of biological chemistry.

[21]  C. Yanofsky,et al.  Purification and characterization of trp aporepressor. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[22]  A. Zeng,et al.  Model analysis concerning the effects of growth rate and intracellular tryptophan level on the stability and dynamics of tryptophan biosynthesis in bacteria , 1997 .

[23]  B. T. Koh,et al.  Genetically structured mathematical modeling of trp attenuator mechanism. , 1998, Biotechnology and bioengineering.

[24]  R. D. Bliss,et al.  Role of feedback inhibition in stabilizing the classical operon. , 1982, Journal of theoretical biology.