Near-critical behavior of aminoacyl-tRNA pools in E. coli at rate limiting supply of amino acids

¹ Uppsala University

^* To whom correspondence should be addressed. E-mail: ehrenberg{at}xray.bmc.uu.se.

Submitted on August 13, 2004
Revised on September 11, 2004
Accepted on 19 October 2004

	Abstract

The rates of consumption of different amino acids in protein synthesis are in general stoichiometrically coupled with coefficients determined by codon usage frequencies on translating ribosomes. We show that when the rates of synthesis of two or more amino acids are limiting for protein synthesis and exactly matching their coupled rates of consumption on translating ribosomes, the pools of aminoacyl-tRNAs in ternary complex with elongation factor Tu and GTP are hyper-sensitive to a variation in the rate of amino acid supply. This high sensitivity makes a macroscopic analysis inconclusive, since it is accompanied by almost free and anti-correlated diffusion in copy numbers of ternary complexes. This near-critical behavior is relevant for balanced growth of E. coli cells in media that lack amino acids and for adaptation of E. coli cells after downshifts from amino acid containing to amino acid lacking growth media. The theoretical results are used to discuss transcriptional control of amino acid synthesis during multiple amino acid limitation, the recovery of E. coli cells after nutritional downshifts and to propose a robust mechanism for the regulation of RelA-dependent synthesis of the global effector molecule ppGpp.

Key Words: biosynthesis, flow, fluctuations, near-critical, protein synthesis, tRNA