| Autor: |
Liao C; Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Program for Computational and Systems Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States., Priyanka P; Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States., Lai YH; Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States., Rao CV; Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States., Lu T; Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Department of Physics, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States.; Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, United States. |
| Abstrakt: |
Microorganisms are shown to actively partition their intracellular resources, such as proteins, for growth optimization. Recent experiments have begun to reveal molecular components unpinning the partition; however, quantitatively, it remains unclear how individual parts orchestrate to yield precise resource allocation that is both robust and dynamic. Here, we developed a coarse-grained mathematical framework that centers on guanosine pentaphosphate (ppGpp)-mediated regulation and used it to systematically uncover the design principles of proteome allocation in Escherichia coli . Our results showed that the cellular ability of resource partition lies in an ultrasensitive, negative feedback-controlling topology with the ultrasensitivity arising from zero-order amino acid kinetics and the negative feedback from ppGpp-controlled ribosome synthesis. In addition, together with the time-scale separation between slow ribosome kinetics and fast turnovers of ppGpp and amino acids, the network topology confers the organism an optimization mechanism that mimics sliding mode control, a nonlinear optimization strategy that is widely used in man-made systems. We further showed that such a controlling mechanism is robust against parameter variations and molecular fluctuations and is also efficient for biomass production over time. This work elucidates the fundamental controlling mechanism of E. coli proteome allocation, thereby providing insights into quantitative microbial physiology as well as the design of synthetic gene networks. |
