The most common way for microbes to control their metabolism is by controlling enzyme levels through transcriptional regulation. Yet recent studies have shown that in many cases, perturbations to the transcriptional regulatory network do not result in altered metabolic phenotypes on the level of the flux distribution. We suggest that this may be a consequence of cells protecting their metabolism against stochastic fluctuations in expression as well as enabling a fast response for those fluxes that may need to be changed quickly. Furthermore, it is impossible for a regulatory program to guarantee optimal expression levels in all conditions. Several studies have found examples of demonstrably suboptimal regulation of gene expression, and improvements to the regulatory network have been investigated in laboratory evolution experiments.
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