Colibactin

Last updated
Colibactin
Colibactin.svg
Names
IUPAC name
2-[6-[(2S)-2-methyl-3,4-dihydro-2H-pyrrol-5-yl]-5-oxo-4-azaspiro[2.4]hept-6-en-7-yl]-N-[[4-[2-[4-[2-[[2-[6-[(2S)-2-methyl-3,4-dihydro-2H-pyrrol-5-yl]-5-oxo-4-azaspiro[2.4]hept-6-en-7-yl]acetyl]amino]acetyl]-1,3-thiazol-2-yl]-2-oxoacetyl]-1,3-thiazol-2-yl]methyl]acetamide
Identifiers
3D model (JSmol)
ChEBI
PubChem CID
  • InChI=1S/C37H38N8O7S2/c1-17-3-5-21(40-17)29-19(36(7-8-36)44-33(29)51)11-26(47)38-13-25(46)23-15-54-35(43-23)32(50)31(49)24-16-53-28(42-24)14-39-27(48)12-20-30(22-6-4-18(2)41-22)34(52)45-37(20)9-10-37/h15-18H,3-14H2,1-2H3,(H,38,47)(H,39,48)(H,44,51)(H,45,52)/t17-,18-/m0/s1
    Key: ZWKHDAZPVITMAI-ROUUACIJSA-N
  • C[C@H]1CCC(=N1)C2=C(C3(CC3)NC2=O)CC(=O)NCC4=NC(=CS4)C(=O)C(=O)C5=NC(=CS5)C(=O)CNC(=O)CC6=C(C(=O)NC67CC7)C8=N[C@H](CC8)C
Properties
C37H38N8O7S2
Molar mass 770.88 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Colibactin is a genotoxic metabolite produced by Escherichia coli and other Enterobacteriaceae ("enteric bacteria") believed to cause mutations leading to colorectal cancer and the progression of colorectal cancer. [1] [2] [3] [4] Colibactin is a polyketide peptide that can form interstrand crosslinks in DNA. [2] Colibactin is only produced by bacterial strains containing a polyketide synthase genomic island (pks) [1] or clb biosynthetic gene cluster. [4] About 20% of humans are colonized with E. coli that harbor the pks island. [5]

Colibactin forms DNA inter-strand cross-links by alkylation of adenine moieties on opposing DNA strands. [4] It induces lytic development in certain bacteria that contain prophages. [6]

Related Research Articles

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Enterobacteria phage λ is a bacterial virus, or bacteriophage, that infects the bacterial species Escherichia coli. It was discovered by Esther Lederberg in 1950. The wild type of this virus has a temperate life cycle that allows it to either reside within the genome of its host through lysogeny or enter into a lytic phase, during which it kills and lyses the cell to produce offspring. Lambda strains, mutated at specific sites, are unable to lysogenize cells; instead, they grow and enter the lytic cycle after superinfecting an already lysogenized cell.

<i>Escherichia coli</i> Enteric, rod shaped, gram-negative bacterium

Escherichia coli, also known as E. coli, is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes (EPEC, ETEC etc.) can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. The harmless strains are part of the normal microbiota of the gut, and can benefit their hosts by producing vitamin K2, and preventing colonisation of the intestine with pathogenic bacteria, having a mutualistic relationship. E. coli is expelled into the environment within fecal matter. The bacterium grows massively in fresh fecal matter under aerobic conditions for three days, but its numbers decline slowly afterwards.

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FtsZ Protein encoded by the ftsZ gene

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Filamentation

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Fic/DOC protein family

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References

  1. 1 2 Arthur JC (2020). "Microbiota and colorectal cancer: colibactin makes its mark". Nature Reviews Gastroenterology & Hepatology . 17 (6): 317–318. doi:10.1038/s41575-020-0303-y. PMID   32317778. S2CID   216033220.
  2. 1 2 Zhou T, Hirayama Y, Watanabe K (2021). "Isolation of New Colibactin Metabolites from Wild-Type Escherichia coli and In Situ Trapping of a Mature Colibactin Derivative". Journal of the American Chemical Society . 143 (14): 5526–5533. doi:10.1021/jacs.1c01495. PMID   33787233.
  3. Helmink BA, Khan M, Wargo JA (2019). "The microbiome, cancer, and cancer therapy". Nature Medicine . 25 (3): 377–388. doi:10.1038/s41591-019-0377-7. PMID   30842679. S2CID   71145949.
  4. 1 2 3 Wernke KM, Xue M, Herzon SB (2020). "Structure and bioactivity of colibactin". Bioorganic & Medicinal Chemistry Letters . 30 (15): 127280. doi:10.1016/j.bmcl.2020.127280. PMC   7309967 . PMID   32527463.
  5. Balskus EP (2015). "Colibactin: understanding an elusive gut bacterial genotoxin". Natural Product Reports. 32 (11): 1534–40. doi:10.1039/c5np00091b. PMID   26390983.
  6. Silpe, Justin E.; Wong, Joel W. H.; Owen, Siân V.; Baym, Michael; Balskus, Emily P. (2022-02-23). "The bacterial toxin colibactin triggers prophage induction". Nature: 1–6. doi:10.1038/s41586-022-04444-3. ISSN   1476-4687. PMID   35197633.