On the robust circuit design schemes of biochemical networks: Steady-state approach

Based on the steady-state analyses of the synergism and saturation system (S-system) model, a robust control method is proposed for biochemical networks via feedback and feedforward biochemical circuits. Two robust biochemical circuit design schemes are developed. One scheme is to improve the system's structural stability so as to tolerate larger kinetic parameter variations, whereas the other is to compensate for the kinetic parameter variations to eliminate their effects. In addition, a multi-objective biochemical circuit design scheme is introduced for both the robust design against kinetic parameter variations and a desired sensitivity design to eliminate the effect of external disturbance simultaneously. The proposed robust circuit design schemes will provide a systematic method with potential applications in synthetic circuit design for biotechnological purpose and drug design purpose. Recent advances in both metabolic and genetic engineering have made the robust biochemical circuit control approach feasible through the design and implementation of synthetic biological networks amenable to mathematical modeling and quantitative analysis. Finally, several examples including the robust circuit design of the tricarboxylic acid cycle are used in silico to illustrate the design procedure and to confirm the performance of the proposed design method.