How Does Escherichia coli Allocate Proteome?

Area of Science:

• Microbial Physiology
• Systems Biology
• Biophysics

Background:

• Microorganisms actively partition intracellular resources for growth optimization.
• The molecular mechanisms and quantitative principles of this resource allocation remain unclear.

Purpose of the Study:

• To develop a mathematical framework to uncover design principles of proteome allocation in Escherichia coli.
• To elucidate the role of guanosine pentaphosphate (ppGpp)-mediated regulation in resource partitioning.

Main Methods:

• Developed a coarse-grained mathematical framework.
• Focused on guanosine pentaphosphate (ppGpp)-mediated regulation.
• Analyzed proteome allocation in Escherichia coli.

Main Results:

• Identified an ultrasensitive, negative feedback-controlling topology for resource partitioning.
• Ultrasensitivity arises from zero-order amino acid kinetics and negative feedback from ppGpp-controlled ribosome synthesis.
• The network topology confers a sliding mode control-like optimization mechanism, robust against variations and efficient for biomass production.

Conclusions:

• Elucidated the fundamental controlling mechanism of E. coli proteome allocation.
• Provided insights into quantitative microbial physiology and synthetic gene network design.
• Demonstrated a robust and efficient resource allocation strategy mimicking nonlinear optimization.