Extensive regulation of enzyme activity by phosphorylation in Escherichia coli

Schastnaya, Evgeniya; Raguz Nakic, Zrinka; Gruber, Christoph H.; Doubleday, Peter Francis; Krishnan, Aarti; Johns, Nathan I.; Park, Jimin; Wang, Harris H.; Sauer, Uwe

doi:10.1038/s41467-021-25988-4

Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-25901

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	Extensive regulation of enzyme activity by phosphorylation in Escherichia coli
Authors:	Schastnaya, Evgeniya Raguz Nakic, Zrinka Gruber, Christoph H. Doubleday, Peter Francis Krishnan, Aarti Johns, Nathan I. Park, Jimin Wang, Harris H. Sauer, Uwe
et. al:	No
DOI:	10.1038/s41467-021-25988-4 10.21256/zhaw-25901
Published in:	Nature Communications
Volume(Issue):	12
Issue:	5650
Issue Date:	2021
Publisher / Ed. Institution:	Nature Publishing Group
ISSN:	2041-1723
Language:	English
Subjects:	Escherichia coli; Protein; Phosphorylation; Proteomics; Biology; Chemistry; Metabolism; Enzyme
Subject (DDC):	571: Physiology and related subjects 579: Microbiology
Abstract:	Protein serine/threonine/tyrosine (S/T/Y) phosphorylation is an essential and frequent post-translational modification in eukaryotes, but historically has been considered less prevalent in bacteria because fewer proteins were found to be phosphorylated and most proteins were modified to a lower degree. Recent proteomics studies greatly expanded the phosphoproteome of Escherichia coli to more than 2000 phosphorylation sites (phosphosites), yet mechanisms of action were proposed for only six phosphosites and fitness effects were described for 38 phosphosites upon perturbation. By systematically characterizing functional relevance of S/T/Y phosphorylation in E. coli metabolism, we found 44 of the 52 mutated phosphosites to be functional based on growth phenotypes and intracellular metabolome profiles. By effectively doubling the number of known functional phosphosites, we provide evidence that protein phosphorylation is a major regulation process in bacterial metabolism. Combining in vitro and in vivo experiments, we demonstrate how single phosphosites modulate enzymatic activity and regulate metabolic fluxes in glycolysis, methylglyoxal bypass, acetate metabolism and the split between pentose phosphate and Entner-Doudoroff pathways through mechanisms that include shielding the substrate binding site, limiting structural dynamics, and disrupting interactions relevant for activity in vivo.
URI:	https://digitalcollection.zhaw.ch/handle/11475/25901
Fulltext version:	Published version
License (according to publishing contract):	CC BY 4.0: Attribution 4.0 International
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:	Publikationen Life Sciences und Facility Management

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Schastnaya, E., Raguz Nakic, Z., Gruber, C. H., Doubleday, P. F., Krishnan, A., Johns, N. I., Park, J., Wang, H. H., & Sauer, U. (2021). Extensive regulation of enzyme activity by phosphorylation in Escherichia coli. Nature Communications, 12(5650). https://doi.org/10.1038/s41467-021-25988-4

Schastnaya, E. et al. (2021) ‘Extensive regulation of enzyme activity by phosphorylation in Escherichia coli’, Nature Communications, 12(5650). Available at: https://doi.org/10.1038/s41467-021-25988-4.

E. Schastnaya et al., “Extensive regulation of enzyme activity by phosphorylation in Escherichia coli,” Nature Communications, vol. 12, no. 5650, 2021, doi: 10.1038/s41467-021-25988-4.

SCHASTNAYA, Evgeniya, Zrinka RAGUZ NAKIC, Christoph H. GRUBER, Peter Francis DOUBLEDAY, Aarti KRISHNAN, Nathan I. JOHNS, Jimin PARK, Harris H. WANG und Uwe SAUER, 2021. Extensive regulation of enzyme activity by phosphorylation in Escherichia coli. Nature Communications. 2021. Bd. 12, Nr. 5650. DOI 10.1038/s41467-021-25988-4

Schastnaya, Evgeniya, Zrinka Raguz Nakic, Christoph H. Gruber, Peter Francis Doubleday, Aarti Krishnan, Nathan I. Johns, Jimin Park, Harris H. Wang, and Uwe Sauer. 2021. “Extensive Regulation of Enzyme Activity by Phosphorylation in Escherichia Coli.” Nature Communications 12 (5650). https://doi.org/10.1038/s41467-021-25988-4.

Schastnaya, Evgeniya, et al. “Extensive Regulation of Enzyme Activity by Phosphorylation in Escherichia Coli.” Nature Communications, vol. 12, no. 5650, 2021, https://doi.org/10.1038/s41467-021-25988-4.