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Cells employ various mechanisms for dynamic control of enzyme expression. An important mechanism is mutual feedback-or crosstalk-between transcription and metabolism. As recently suggested, enzyme levels are often much higher than absolutely needed to maintain metabolic flux. However, given the potential burden of high enzyme levels it seems likely that cells control enzyme expression to meet other cellular objectives. In this review, we discuss whether crosstalk between metabolism and transcription could inform cells about how much enzyme is optimal for various fitness aspects. Two major problems should be addressed in order to understand optimization of enzyme levels by crosstalk. First, mapping of metabolite-protein interactions will be crucial to obtain a better mechanistic understanding of crosstalk. Second, investigating cellular objectives that define optimal enzyme levels can reveal the functional relevance of crosstalk. We present recent studies that approach these problems, drawing from experimental transcript and metabolite data, and from theoretical network analyses. WIREs Syst Biol Med 2018, 10:e1396. doi: 10.1002/wsbm.1396 This article is categorized under: Biological Mechanisms > Metabolism Laboratory Methods and Technologies > Metabolomics Biological Mechanisms > Regulatory Biology.
