Systematic inference of functional phosphorylation events in yeast metabolism.
BACKGROUND
Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification of phosphorylation events on metabolic enzymes, but identifying functional phosphorylation events still requires more detailed biochemical characterization. Therefore, development of computational methods for investigating unknown functions of a large number of phosphorylation events identified by phosphoproteomics has received increased attention.


RESULTS
We developed a mathematical framework that describes the relationship between phosphorylation level of a metabolic enzyme and the corresponding flux through the enzyme. Using this framework, it is possible to quantitatively estimate contribution of phosphorylation events to flux changes. We showed that phosphorylation regulation analysis, combined with a systematic workflow and correlation analysis, can be used for inference of functional phosphorylation events in steady and dynamic conditions, respectively. Using this analysis, we assigned functionality to phosphorylation events of 17 metabolic enzymes in the yeast Saccharomyces cerevisiae , among which 10 are novel. Phosphorylation regulation analysis cannot only be extended for inference of other functional post-translational modifications but also be a promising scaffold for multi-omics data integration in systems biology.


METHODS
Matlab codes for flux balance analysis in this study are available in Supplementary material.


BACKGROUND
yhwang@ecust.edu.cn or nielsenj@chalmers.se.


BACKGROUND
Supplementary data are available at Bioinformatics online.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.|Department of Biology and Biological Engineering, Chalmers University of Technology, SE412 96 Gothenburg, Sweden.
Yu
Y
Chen
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
Yonghong
Y
Wang
Department of Biology and Biological Engineering, Chalmers University of Technology, SE412 96 Gothenburg, Sweden.|Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby DK2800, Denmark.
Jens
J
Nielsen
D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012984:Software
D029701:Saccharomyces cerevisiae Proteins