Global regulation of protein phosphorylation and dephosphorylation plays crucial roles in various cellular processes, serving as a fundamental mechanism for regulating protein function, cell metabolic performance and stress response. In response to differences in nutrition, alterations in the metabolic flux are accompanied by the changes in the phosphorylation levels of enzymes. However, the stress-driven large-scale protein phosphorylation in cells and the underlying principles remain unclear. Here, we report a global switchable phosphorylation pattern of yeast cells in response to environmental variations, which is governed reversibly with one bifunction phosphatase regulator, Ykr075c. We found this regulator could change the phosphorylation pattern of proteins, covering carbon metabolism and signal transduction, and thus greatly enhancing the growth and cell metabolism under the heat stress. As reasons, it dephosphorylates glycogen synthesis enzymes and affects enzyme activities as well, and it also mediates the dephosphorylation of several protein kinases and glucose metabolism-related transcription factors, thereby elevating carbon metabolism at the transcriptional level. Based on these findings, we significantly enhanced the growth and production of yeast cells, exhibiting the universality across variable products and diverse species and offering novel insights into the regulation of protein phosphorylation for designing microbial cell factories.