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Cited by 11Metal-Catalyzed Oxygenation MechanismsRedox biology and oxidative stressMetalloenzymes and iron-sulfur proteins

Microbes vary strategically in their metalation of mononuclear enzymes

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Rohaun, Sanjay Kumar, Sethu, Ramakrishnan, Imlay, James A.·2024·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2401738121PMC PMC11127058
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Abstract

Studies have determined that nonredox enzymes that are cofactored with Fe(II) are the most oxidant-sensitive targets inside Escherichia coli . These enzymes use Fe(II) cofactors to bind and activate substrates. Because of their solvent exposure, the metal can be accessed and oxidized by reactive oxygen species, thereby inactivating the enzyme. Because these enzymes participate in key physiological processes, the consequences of stress can be severe. Accordingly, when E. coli senses elevated levels of H 2 O 2 , it induces both a miniferritin and a manganese importer, enabling the replacement of the iron atom in these enzymes with manganese. Manganese does not react with H 2 O 2 and thereby preserves enzyme activity. In this study, we examined several diverse microbes to identify the metal that they customarily integrate into ribulose-5-phosphate 3-epimerase, a representative of this enzyme family. The anaerobe Bacteroides thetaiotaomicron , like E. coli , uses iron. In contrast, Bacillus subtilis and Lactococcus lactis use manganese, and Saccharomyces cerevisiae uses zinc. The latter organisms are therefore well suited to the oxidizing environments in which they dwell. Similar results were obtained with peptide deformylase, another essential enzyme of the mononuclear class. Strikingly, heterologous expression experiments show that it is the metal pool within the organism, rather than features of the protein itself, that determine which metal is incorporated. Further, regardless of the source organism, each enzyme exhibits highest turnover with iron and lowest turnover with zinc. We infer that the intrinsic catalytic properties of the metal cannot easily be retuned by evolution of the polypeptide.

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Cited by

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Authors
Rohaun, S. K., Sethu, R., & Imlay, J. A.
Affiliations
  • University of Illinois Urbana-Champaign (US)
  • Department of Microbiology, University of Illinois, Urbana, IL 61801
Corresponding author
  • Rohaun, Sanjay Kumar
  • Imlay, James A.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2024-05-14
Volume
121
Issue
21
Pages
e2401738121-e2401738121
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2401738121
PMC
PMC11127058
OpenAlex
W4396887158
Cited by
11
References
2
Citations by year
2026: 2 · 2025: 6 · 2024: 3
FWCI
1.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
HHS | National Institutes of Health (GM49640)
Topics
  • Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
Keywords
metal cofactors, peptide deformylase, reactive oxygen species, hydrogen peroxide stress, Bacteroides thetaiotaomicron, Bacillus subtilis, Lactococcus lactis, Saccharomyces cerevisiae, enzyme turnover, metal ion specificity, heterologous expression, Escherichia coli
MeSH terms
Bacillus subtilis, Escherichia coli, Hydrogen Peroxide, Iron, Manganese, Metals, Oxidation-Reduction, Saccharomyces cerevisiae, Lactococcus lactis, Zinc

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