Rethinking the Choice Behavior of Sugar Metabolism in Bacteria

Area of Science:

• Microbial Physiology
• Biochemical Engineering
• Systems Biology

Background:

• The cybernetic model explains microbial growth by resource allocation for enzyme synthesis.
• Previous models lacked an explicit economic framework for the cell's decision-making process.
• The optimality of the matching rule was established, but the precise objective and constraints were undefined.

Purpose of the Study:

• To formulate the cybernetic enzyme-synthesis control as an explicit economic decision problem.
• To recast microbial resource allocation as a linear programming problem from microeconomic theory.
• To elucidate the economic basis for sequential versus simultaneous substrate utilization.

Main Methods:

• The cell's proteome budget is treated as a constraint in a linear program (LP).
• Growth utility is maximized subject to the proteome budget, modeled as a linear function.
• LP solutions are analyzed geometrically to determine optimal enzyme allocation strategies.

Main Results:

• The linear programming approach reveals that cells allocate their entire proteome to the most profitable substrate (corner solution), leading to diauxic growth.
• Simultaneous substrate use occurs only in a degenerate case where substrate profitability is equal.
• The LP-derived cybernetic variables accurately predicted the diauxic and triauxic batch growth of *Klebsiella oxytoca*.

Conclusions:

• Sequential substrate use is the standard outcome of growth maximization when resources are perfectly substitutable.
• Simultaneous substrate utilization is a special case arising from equal substrate profitability.
• The economic decision framework provides a robust explanation for observed microbial growth patterns.