Influence of the feedback loops in the trp operon of B. subtilis on the system dynamic response and noise amplitude.
In this paper we introduce a mathematical model for the tryptophan operon regulatory pathway in Bacillus subtilis. This model considers the transcription-attenuation, and the enzyme-inhibition regulatory mechanisms. Special attention is paid to the estimation of all the model parameters from reported experimental data. With the aid of this model we investigate, from a mathematical-modeling point of view, whether the existing multiplicity of regulatory feedback loops is advantageous in some sense, regarding the dynamic response and the biochemical noise in the system. The tryptophan operon dynamic behavior is studied by means of deterministic numeric simulations, while the biochemical noise is analyzed with the aid of stochastic simulations. The model feasibility is tested comparing its stochastic and deterministic results with experimental reports. Our results for the wildtype and for a couple of mutant bacterial strains suggest that the enzyme-inhibition feedback loop, dynamically accelerates the operon response, and plays a major role in the reduction of biochemical noise. Also, the transcription-attenuation feedback loop makes the trp operon sensitive to changes in the endogenous tryptophan level, and increases the amplitude of the biochemical noise.
Centro de Investigación y de Estudios Avanzados del IPN, Unidad Monterrey, Vía del Conocimiento 201, Parque de Investigación e Innovación Tecnológica, 66600 Apodaca NL, Mexico.
Criseida
C
Zamora-Chimal
Moisés
M
Santillán
Jesús
J
Rodríguez-González
D000878:Anthranilate Synthase / Q000235:genetics; D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics*; D003198:Computer Simulation; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D008957:Models, Genetic; D009876:Operon / Q000235:genetics*; D013997:Time Factors; D014364:Tryptophan / Q000235:genetics*
D014364:Tryptophan; D000878:Anthranilate Synthase