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Cited by 12Bacterial Genetics and BiotechnologyBiochemical and Structural CharacterizationEnzyme Structure and Function

Metalation of Extracytoplasmic Proteins and Bacterial Cell Envelope Homeostasis

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He, Bixi, Helmann, John D.·2024·Annual Review of Microbiology
DOI 10.1146/annurev-micro-041522-091507PMC PMC11922083
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Abstract

Cell physiology requires innumerable metalloenzymes supported by the selective import of metal ions. Within the crowded cytosol, most enzymes acquire their cognate cofactors from a buffered labile pool. Metalation of membrane-bound and secreted exoenzymes is more problematic since metal concentrations are highly variable outside the cell. Here, we focus on metalloenzymes involved in cell envelope homeostasis. Peptidoglycan synthesis often relies on Zn-dependent hydrolases, and metal-dependent β-lactamases play important roles in antibiotic resistance. In gram-positive bacteria, lipoteichoic acid synthesis requires Mn, with TerC family Mn exporters in a supporting role. For some exoenzymes, metalation occurs in the cytosol, and metalated enzymes are exported through the TAT secretion system. For others, metalation is facilitated by metal exporters, metallochaperones, or partner proteins that enhance metal affinity. To help ensure function, some metalloenzymes can function with multiple metals. Thus, cells employ a diversity of strategies to ensure metalation of enzymes functioning outside the cytosol.

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  • The bulk of the quota for manganese and iron is devoted to intracellular enzymes, with a variable fraction partitioned to the membrane or to extracellular enzymes, and the latter may require dedicated maturation pathways.

    “The bulk of the quota for manganese and iron is devoted to intracellular enzymes (Figure 3), with a variable fraction partitioned to the membrane (e.g., respiratory complexes) or to extracellular enzymes. The latter may require dedicated pathways for their maturation.95,96”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [96]

    The ‘Metalation of Extracytoplasmic Enzymes’ section describes pathways for maturing exoenzymes, including export after metalation and metal loading outside the cell. The ‘Major Pathways for Metalation of Cytosolic Enzymes’ section says free Mn and Fe are often about 1% of the cellular quota, but does not establish that the bulk is devoted to intracellular enzymes or quantify a variable fraction allocated to membrane and extracellular enzymes. Page numbers are unavailable in our copy. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
He, B., & Helmann, J. D.
Affiliations
Cornell University (US)
Corresponding author
Helmann, John D.
ORCID
Venue
Annual Review of Microbiology
Publisher
Annual Reviews
Published
2024-11-10
Volume
78
Issue
1
Pages
83-102
ISSN
  • 0066-4227 (ISSN-L)
  • 1545-3251
DOI
10.1146/annurev-micro-041522-091507
PMC
PMC11922083
OpenAlex
W4400307800
Cited by
12
References
10
Citations by year
2026: 4 · 2025: 7 · 2024: 1
FWCI
0.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Annual Review of Microbiology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
Funders
  • Agence Nationale de la Recherche (ANR-20-CO11-0001, ANR-18-CE15-0020, ANR-19-CE15-0009, ANR-21-COVR-0039, ANR-20-COVI-0003)
  • National Institutes of Health
  • National Institute of General Medical Sciences (R35GM122461)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords
metallochaperone, peptidoglycan biosynthesis, beta-lactamase, antibiotic resistance, metalloenzymes, Gram-positive bacteria
MeSH terms
Bacteria, Bacterial Proteins, Cell Membrane, Cell Wall, Gram-Positive Bacteria, Homeostasis, Lipopolysaccharides, Metals, Peptidoglycan, Teichoic Acids

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