Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus
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Summary: Siderophores are iron‐scavenging molecules produced by many microbes. In general, they are synthesized using either non‐ribosomal peptide synthetase (NRPS) or NRPS‐independent siderophore (NIS) pathways. Staphylococcus aureus produces siderophores, of which the structures of staphyloferrin A and staphyloferrin B are known. Recently, the NIS biosynthetic pathway for staphyloferrin A was characterized. Here we show that, in S. aureus, the previously identified sbn (s iderophore b iosy n thesis) locus encodes enzymes required for the synthesis of staphyloferrin B, an α‐hydroxycarboxylate siderophore comprised of l‐2,3‐diaminopropionic acid, citric acid, 1,2‐diaminoethane and α‐ketoglutaric acid. Staphyloferrin B NIS biosynthesis was recapitulated in vitro, using purified recombinant Sbn enzymes and the component substrates. In vitro synthesized staphyloferrin B readily promoted the growth of iron‐starved S. aureus, via the ABC transporter SirABC. The SbnCEF synthetases and a decarboxylase, SbnH, were necessary and sufficient to produce staphyloferrin B in reactions containing component substrates l‐2,3‐diaminopropionic acid, citric acid and α‐ketoglutaric acid. Since 1,2‐diaminoethane was not required, this component of the siderophore arises from the SbnH‐dependent decarboxylation of a 2,3‐diaminoproprionic acid‐containing intermediate. Liquid chromatography‐electrospray ionization‐mass spectrometry (LC‐ESI‐MS) analyses of a series of enzyme reactions identified mass ions corresponding to biosynthetic intermediates, allowing for the first proposed biosynthetic pathway for staphyloferrin B.
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Staphyloferrin B is a 448 Da compound composed of L-2,3-diaminopropionic acid, 1,2-diaminoethane, and α-ketoglutaric acid, produced by the sbnABCDEFGHI operon and transported by SirABC.
“Staphyloferrin B is a 448 Da compound composed of L-2,3-diaminopropionic acid, 1,2-diaminoethane, and α-ketoglutaric acid [56]. Staphyloferrin B is a product of the sbnABCDEFGHI operon, of which only SbnC, SbnE, SbnF, and SbnH are required for in vitro synthesis [57]. Transport of staphyloferrin B across the staphylococcal cell membrane is mediated by the staphylococcal iron-regulated transporter”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [57]
Staphyloferrin B synthesis is encoded by the sbnABCDEFGHI operon.
“The synthesis of staphyloferrin B is encoded by the sbnABCDEFGHI operon (14).”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [14]
S. aureus srtA mutants are severely attenuated in a murine abscess model of infection.
“S. aureus srtA mutants are severely attenuated in a murine abscess model of infection (14, 49).”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [14]
Inactivation of isdC causes only a modest decrease in bacterial loads in infected kidneys after five days.
“Similar to the isdA mutant, inactivation of isdC leads to only a modest decrease in bacterial loads in infected kidneys after five days of infection (14).”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [14]
Inactivation of isdA reduces colonization of human skin.
“Inactivation of isdA leads to decreased ability to colonize human skin and a decrease in bacterial load in murine kidneys five days post systemic infection (14, 15).”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [14]
Inactivation of isdA reduces bacterial load in murine kidneys five days after systemic infection.
“Inactivation of isdA leads to decreased ability to colonize human skin and a decrease in bacterial load in murine kidneys five days post systemic infection (14, 15).”
From Molecular Mechanisms of <i>Staphylococcus aureus</i> Iron Acquisition (2011) · cites this paper as [14]
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“The sfa locus (for SA) and the sbn operon (for SB) code for the biosynthesis and efflux of these siderophores by S. aureus (13, 15).”
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- Authors
- Cheung, J., Beasley, F. C., Liu, S., Lajoie, G. A., & Heinrichs, D. E.
- Affiliations
- Western University (CA)
- Corresponding author
- Heinrichs, David E.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2009-10-22
- Volume
- 74
- Issue
- 3
- Pages
- 594-608
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1997955858
- Cited by
- 144
- References
- 33
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 8 · 2022: 9 · 2021: 8 · 2020: 6 · 2019: 12 · 2018: 4 · 2017: 7 · 2016: 7 · 2015: 14 · 2014: 12 · 2013: 4 · 2012: 11
- FWCI
- 5.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Scholarship@Western (Western University) (submittedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- Staphylococcus aureus, siderophore biosynthesis, 2,3-diaminopropionic acid, ethylenediamine, alpha-ketoglutarate, citric acid, iron acquisition, biosynthetic pathway, biosynthetic intermediates
- MeSH terms
- Bacterial Proteins, Citrates, Escherichia coli, Ethylenediamines, Ferric Compounds, Genes, Bacterial, Multigene Family, Iron, Iron Chelating Agents, Ketoglutaric Acids, Ornithine, Peptide Synthases, Staphylococcus aureus, Stereoisomerism, beta-Alanine, Gene Expression Regulation, Bacterial, Siderophores, ATP-Binding Cassette Transporters, Citric Acid
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