Metabolic growth rate control in Escherichia coli may be a consequence of subsaturation of the macromolecular biosynthetic apparatus with substrates and catalytic components

Abstract

In this paper, the Escherichia coli cell is considered as a system designed for rapid growth, but limited by the medium. We propose that this very design causes the cell to become subsaturated with precursors and catalytic components at all levels of macromolecular biosynthesis and leads to a molecular sharing economy at a high level of competition inside the cell. Thus, the promoters compete with each other in the binding of a limited amount of free RNA polymerase and the ribosome binding sites on the mRNA chains compete with each other for the free ribosomes. The macromolecular chain elongation reactions sequester a considerable proportion of the total amount of RNA polymerase and ribosomes in the cells. We propose that the degree of subsaturation of the macromolecular biosynthetic apparatus renders a variable fraction of RNA polymerase and ribosomes unavailable for the initiation of new chain synthesis and that this, at least in part, determines the composition of the cell as a function of the growth rate. Thus, at rapid growth, the high speed of the elongation reactions enables the cell to increase the concentrations of free RNA polymerase and ribosomes for initiation purposes. Furthermore, it is proposed that the speed of RNA polymerase movement is adjusted to the performance speed of the ribosomes. Mechanistically, this adjustment of the coupling between transcription and translation involves transcriptional pause sites along the RNA chains, the adjustment of the saturation level of RNA polymerase with the nucleoside triphosphate substrates, and the concentration of ppGpp, which is known to inhibit RNA chain elongation. This model is able to explain the stringent response and the control of stable RNA and of ribosome synthesis in steady states and in shifts, as well as the rate of overall protein synthesis as a function of the growth rate.