Large scale kinetic modeling of metabolic networks

Problems:
While the biochemistry of metabolism in many organisms is well studied, details of the metabolic dynamics are yet fully explored.

Unless the parameters of a vast number of enzyme-catalyzed reactions happened to fall into very special ranges, a kinetic model on a large metabolic network would fail to reach a steady state.

Acquiring adequate in vivo kinetic parameters experimentally has always been an obstacle.

Approach:
A stable metabolic network can be systematically established via a biologically/evolutionally motivated regulatory process.

May be understood via a landscape description of metabolism as a stochastic system, which draws enzymatic parameters towards stable phase spaces.

Allows explicit thermodynamics constraints on concentrations and optimal balance of efficiency vs viability (i.e. stability/fitness/robustness).

The strategy was applied sucessfully to the central metabolism of Methylobacterium extorquens AM1 and the secondary metabolism and metabolic switches in Streptomyces xiamenensis 318.