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PreprintCited by 20Microbial Metabolic Engineering and BioproductionGene Regulatory Network AnalysisBioinformatics and Genomic Networks

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Metabolic signatures of regulation by phosphorylation and acetylation

Open access
Smith, Kirk, Shen, Fangzhou, Lee, Ho Joon, Chandrasekaran, Sriram·2019·iScience
DOI 10.1101/838243PMC PMC8762462

Preprint — published as 10.1016/j.isci.2021.103730

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Abstract

Acetylation and phosphorylation are highly conserved post-translational modifications (PTMs) that regulate cellular metabolism, yet how metabolic control is shared between these PTMs is unknown. Here we analyze transcriptome, proteome, acetylome, and phosphoproteome datasets in E.coli , S.cerevisiae , and mammalian cells across diverse conditions using CAROM, a new approach that uses genome-scale metabolic networks and machine-learning to classify regulation by PTMs. We built a single machine-learning model that accurately distinguished reactions controlled by each PTM in a condition across all three organisms based on reaction attributes (AUC>0.8). Our model uncovered enzymes regulated by phosphorylation during a mammalian cell-cycle, which we validate using phosphoproteomics. Interpreting the machine-learning model using game-theory uncovered enzyme properties including network connectivity, essentiality, and condition-specific factors such as maximum flux that differentiate regulation by phosphorylation from acetylation. The conserved and predictable partitioning of metabolic regulation identified here between these PTMs can enable rational engineering of regulatory circuits. Graphical Abstract:

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Metadata

Authors
Smith, K., Shen, F., Lee, H. J., & Chandrasekaran, S.
Affiliations
  • University of Michigan (US)
  • Yale University (US)
Corresponding author
Chandrasekaran, Sriram
ORCID
Venue
iScience
Publisher
openRxiv
Published
2019-11-11
Volume
25
Issue
1
Pages
103730-103730
ISSN
2589-0042 (ISSN-L)
DOI
10.1101/838243
PMC
PMC8762462
OpenAlex
W4226038902
Cited by
20
References
1
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 1 · 2021: 4
FWCI
1.06
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • iScience (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Camille and Henry Dreyfus Foundation (R35 GM13779501)
  • University of Michigan
  • National Institutes of Health (R35 GM13779501, GM13779501)
  • National Institute of General Medical Sciences (R35 GM13779501)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
phosphorylation, acetylation, post-translational modification, metabolic regulation, genome-scale metabolic networks, phosphoproteomics, acetylome, cell cycle, Escherichia coli, Saccharomyces cerevisiae, mammalian cells, essentiality, maximum flux

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