Abstract
Background: Robustness plays an important role in the fail-safe mechanism of biochemical networks. A robust biochemical network should be able to cope with environmental changes, not be sensitive to kinetic parameter variations and have a slow rate of degradation of the system function. Therefore, for a biochemical network that lacks robustness to tolerate kinetic parameter variations and environmental changes, it is desirable to have an efficient control design to improve its robustness. Since there does not exist a systematic design method for this purpose, it is highly desirable to develop such a robust circuit control design method. Results: In this study, based on the steady state analyses of the synergism and saturation system (S-system) model, a robust control method is proposed via feedback and feedforward biochemical circuits. Two robust biochemical circuit design schemes are developed. One scheme is to improve the system structure stability to tolerate larger kinetic parameter variations, whereas the other is to compensate for the kinetic parameter variations to eliminate their effect. In addition, a multi-objective biochemical circuit control 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. Using the proposed systematic control method, a biochemical network can be designed to possess a desired robustness to tolerate kinetic parameter variations and a desired sensitivity to efficiently attenuate the effect of environmental disturbances. Conclusions: The proposed control design scheme for a biochemical network will provide a systematic robust circuit design method with a 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 computational simulation examples of robust circuit design including the robust design of the TCA cycle are used to illustrate the design procedure and for the performance confirmation of the proposed design method.