Biological Interpretation of Model-Reference Adaptive Control in a Mass Action Kinetics Metabolic Pathway Model.

The usefulness of control theory to model robustness in metabolic pathways is limited because controller properties and their implications on pathway regulation are unclear. Using sphingolipid biosynthesis in response to single-gene overexpression as a case study, we apply model-reference adaptive control (MRAC) to model regulation in a mass action kinetics pathway model and report on its properties. Tracking error between treated cells (plant) and wild type (reference) is reduced in 9 of 10 system variables compared to using mass action kinetics only. This result is robust when system parameters are perturbed. Furthermore, we interpret control dynamics to infer potential regulatory interactions. Some observations are consistent with independent studies on the effects of the same experimental treatment, while others represent novel hypotheses that may be tested to yield additional biological insight. The usefulness and interpretation of MRAC to model metabolic pathway regulation is shown where plant dynamics approach the reference.