bosdriesz2

vAAsynt1

vAAsynt1

∅ = aa1

vAAsynt10

vAAsynt10

∅ = aa10

vAAsynt11

vAAsynt11

∅ = aa11

vAAsynt12

vAAsynt12

∅ = aa12

vAAsynt13

vAAsynt13

∅ = aa13

vAAsynt14

vAAsynt14

∅ = aa14

vAAsynt15

vAAsynt15

∅ = aa15

vAAsynt16

vAAsynt16

∅ = aa16

vAAsynt17

vAAsynt17

∅ = aa17

vAAsynt18

vAAsynt18

∅ = aa18

vAAsynt19

vAAsynt19

∅ = aa19

vAAsynt2

vAAsynt2

∅ = aa2

vAAsynt20

vAAsynt20

∅ = aa20

vAAsynt3

vAAsynt3

∅ = aa3

vAAsynt4

vAAsynt4

∅ = aa4

vAAsynt5

vAAsynt5

∅ = aa5

vAAsynt6

vAAsynt6

∅ = aa6

vAAsynt7

vAAsynt7

∅ = aa7

vAAsynt8

vAAsynt8

∅ = aa8

vAAsynt9

vAAsynt9

∅ = aa9

vbiomass

vbiomass

{0.05}taa9 + {0.05}taa8 + {0.05}taa7 + {0.05}taa6 + {0.05}taa5 + {0.05}taa4 + {0.05}taa3 + {0.05}taa20 + {0.05}taa2 + {0.05}taa19 + {0.05}taa18 + {0.05}taa17 + {0.05}taa16 + {0.05}taa15 + {0.05}taa14 + {0.05}taa13 + {0.05}taa12 + {0.05}taa11 + {0.05}taa10 + {0.05}taa1 = ∅

vtRNAchar1

vtRNAchar1

aa1 = taa1

vtRNAchar10

vtRNAchar10

aa10 = taa10

vtRNAchar11

vtRNAchar11

aa11 = taa11

vtRNAchar12

vtRNAchar12

aa12 = taa12

vtRNAchar13

vtRNAchar13

aa13 = taa13

vtRNAchar14

vtRNAchar14

aa14 = taa14

vtRNAchar15

vtRNAchar15

aa15 = taa15

vtRNAchar16

vtRNAchar16

aa16 = taa16

vtRNAchar17

vtRNAchar17

aa17 = taa17

vtRNAchar18

vtRNAchar18

aa18 = taa18

vtRNAchar19

vtRNAchar19

aa19 = taa19

vtRNAchar2

vtRNAchar2

aa2 = taa2

vtRNAchar20

vtRNAchar20

aa20 = taa20

vtRNAchar3

vtRNAchar3

aa3 = taa3

vtRNAchar4

vtRNAchar4

aa4 = taa4

vtRNAchar5

vtRNAchar5

aa5 = taa5

vtRNAchar6

vtRNAchar6

aa6 = taa6

vtRNAchar7

vtRNAchar7

aa7 = taa7

vtRNAchar8

vtRNAchar8

aa8 = taa8

vtRNAchar9

vtRNAchar9

aa9 = taa9

Global parameters

Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.


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How fast-growing bacteria robustly tune their ribosome concentration to approximate growth-rate maximization.

  • Evert Bosdriesz
  • Douwe Molenaar
  • Bas Teusink
  • Frank J Bruggeman
FEBS J. 2015; 282 (10): 2029-2044
Abstract
Maximization of growth rate is an important fitness strategy for bacteria. Bacteria can achieve this by expressing proteins at optimal concentrations, such that resources are not wasted. This is exemplified for Escherichia coli by the increase of its ribosomal protein-fraction with growth rate, which precisely matches the increased protein synthesis demand. These findings and others have led to the hypothesis that E. coli aims to maximize its growth rate in environments that support growth. However, what kind of regulatory strategy is required for a robust, optimal adjustment of the ribosome concentration to the prevailing condition is still an open question. In the present study, we analyze the ppGpp-controlled mechanism of ribosome expression used by E. coli and show that this mechanism maintains the ribosomes saturated with its substrates. In this manner, overexpression of the highly abundant ribosomal proteins is prevented, and limited resources can be redirected to the synthesis of other growth-promoting enzymes. It turns out that the kinetic conditions for robust, optimal protein-partitioning, which are required for growth rate maximization across conditions, can be achieved with basic biochemical interactions. We show that inactive ribosomes are the most suitable 'signal' for tracking the intracellular nutritional state and for adjusting gene expression accordingly, as small deviations from optimal ribosome concentration cause a huge fractional change in ribosome inactivity. We expect to find this control logic implemented across fast-growing microbial species because growth rate maximization is a common selective pressure, ribosomes are typically highly abundant and thus costly, and the required control can be implemented by a small, simple network.

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