Flux control through protein phosphorylation in yeast

Protein phosphorylation is one of the most important mechanisms regulating metabolism as it can directly modify metabolic enzymes by the addition of phosphate groups. Attributed to such a rapid and reversible mechanism, cells can adjust metabolism rapidly in response to temporal changes. The yeast Saccharomyces cerevisiae, a widely used cell factory and model organism, is reported to show frequent phosphorylation events in metabolism. Studying protein phosphorylation in S. cerevisiae allows for gaining new insight into the function of regulatory networks, which may enable improved metabolic engineering as well as identify mechanisms underlying human metabolic diseases. Here we collect functional phosphorylation events of 41 enzymes involved in yeast metabolism and demonstrate functional mechanisms and the application of this information in metabolic engineering. From a systems biology perspective, we describe the development of phosphoproteomics in yeast as well as approaches to analysing the phosphoproteomics data. Finally, we focus on integrated analyses with other omics data sets and genome-scale metabolic models. Despite the advances, future studies improving both experimental technologies and computational approaches are imperative to expand the current knowledge of protein phosphorylation in S. cerevisiae.