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A novel analysis and synthesis framework is devised for synergism and saturation system, commonly known as S-system, for improving the robustness of the TCA cycle. In order to minimize the perturbation sensitivity, a measure of robustness of the network, a new design framework is proposed. The design constraints are formulated in computationally attractive convex optimization framework. The proposed multi-objective optimization problem, framed as Linear Matrix Inequality (LMI), makes a trade-off between the robustness and the control effort of the synthesized TCA cycle.