Surplus of central biosynthetic components benefits physiological adaptation in Escherichia coli

Bacterial cells exhibit distinct physiological states in different environments and transition between them without genetic changes. Fast growth under steady conditions and rapid physiological adaptation to a new environment are both essential for improving cell fitness. While the control of steady-state growth has been extensively studied in bacteria, we still need a better understanding of what determines cell behavior during non-genetic physiological adaptation to a new environment.

Here, we test the cellular surplus hypothesis – an essential biosynthetic component may possess an excess amount that does not enhance steady growth but rather is beneficial for adaptation to a new environment. By measuring titratable gene expression levels and steady-state growth rate using single-cell microfluidics, we find that the tested essential biosynthetic components in E. coli all have a predominantly large surplus when growing in nutrient-poor conditions, such as those involved in central metabolism, transcription, and translation. Perturbation of the surplus in transcription and translation results in a significant slowdown in adapting cell growth to a nutrient-rich condition. Without the surplus, RNA polymerases and ribosome components could become more rate-limiting within the autocatalytic biosynthesis network of the cell, as suggested by our quantitative model and validated by experimental tests. Interestingly, the surplus of tested metabolic enzymes does not benefit the growth adaptation, suggesting their non-rate-limiting role during the nutrient shift.

Our work demonstrates that the surplus is a basic feature of essential cellular components, suggesting condition-dependent limiting factors for central biosynthesis and a fundamental trade-off between the control of steady growth and physiological adaptation. Implementing the concept of surplus into cell modeling and engineering could provide better strategies for optimization of cell fitness and specification of desired cellular functions, with potential applicability in other bacteria and higher organisms.