Characterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow

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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 coll. 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.
Publisher
NATL ACAD SCIENCES
Issue Date
2018-10
Language
English
Article Type
Article
Keywords

CONSTRAINT-BASED MODELS; ESCHERICHIA-COLI; MICROBIAL-METABOLISM; LYSINE ACETYLATION; GENE-EXPRESSION; AMBER; PHOSPHOPROTEOME; IDENTIFICATION; TRANSALDOLASE; ADAPTATION

Citation

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.115, no.43, pp.11096 - 11101

ISSN
0027-8424
DOI
10.1073/pnas.1811971115
URI
http://hdl.handle.net/10203/246527
Appears in Collection
BS-Journal Papers(저널논문)
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