Characterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow

Elizabeth Brunk, Roger L. Chang, Jing Xia, Hooman Hefzi, James T. Yurkovich, Donghyuk Kim, Evan Buckmiller, Harris H. Wang, Byung Kwan Cho, Chen Yang, Bernhard O. Palsson, George M. Church, Nathan E. Lewis

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Understanding the complex interactions of protein posttranslational modifications (PTMs) represents a major challenge in metabolic engineering, synthetic biology, and the biomedical sciences. Here, we present a workflow that integrates multiplex automated genome editing (MAGE), genome-scale metabolic modeling, and atomistic molecular dynamics to study the effects of PTMs on metabolic enzymes and microbial fitness. This workflow incorporates complementary approaches across scientific disciplines; provides molecular insight into how PTMs influence cellular fitness during nutrient shifts; and demonstrates how mechanistic details of PTMs can be explored at different biological scales. As a proof of concept, we present a global analysis of PTMs on enzymes in the metabolic network of Escherichia coli. Based on our workflow results, we conduct a more detailed, mechanistic analysis of the PTMs in three proteins: enolase, serine hydroxymethyltransferase, and transaldolase. Application of this workflow identified the roles of specific PTMs in observed experimental phenomena and demonstrated how individual PTMs regulate enzymes, pathways, and, ultimately, cell phenotypes.

Original languageEnglish (US)
Pages (from-to)11096-11101
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number43
DOIs
StatePublished - Oct 23 2018
Externally publishedYes

Keywords

  • Metabolism
  • Omics data
  • Posttranslational modifications
  • Protein chemistry
  • Systems biology

ASJC Scopus subject areas

  • General

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