Gene Expression Depends on the Interplay Among Growth, Resource Biogenesis, and Nutrient Quality.

The gene expression capacity of bacteria depends on the interplay between growth and the availability of the transcriptional and translational machinery. Growth rate is accepted as the physiological parameter controlling the allocation of cellular resources. Understanding the relationship between growth and resources is key for the efficient design of genetic constructs, but it is obscured by the mutual dependence between growth and gene expression. In this work, we investigate the contributions of molecular factors, growth rate, and metabolism to gene expression by investigating the behavior of bacterial cells grown in chemostats. Using a model of the whole cell and validating it experimentally, our results show that while growth rate and molecular factors, such as the number of rRNA operons, set the abundance of transcriptional and translational machinery, it is metabolism that governs the usage of resources by tuning elongation rates. We show, using a biotechnologically relevant example, that gene expression capacity can be maximized using low growth in a high-quality medium. These findings unveil fundamental trade-offs in physiology that will inform future bioprocess optimization.