Colibactin
{{Chembox
| ImageFile = Colibactin.svg
| ImageSize = 250px
| IUPACName = 2-[6-[(2S)-2-methyl-3,4-dihydro-2H-pyrrol-5-yl]-5-oxo-4-azaspiro[2.4]hept-6-en-7-yl]-N-[
|Section1={{Chembox Identifiers
| ChEBI = 156303
| ChemSpiderID = 115010508
| KEGG = C22668
| PubChem = 138805674
| StdInChI=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
| StdInChIKey = ZWKHDAZPVITMAI-ROUUACIJSA-N
| SMILES = 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
}}
|Section2={{Chembox Properties
| C=37|H=38|N=8|O=7|S=2
}}
|Section8={{Chembox Related
}}
}}
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,{{cite journal | author=Arthur JC | title=Microbiota and colorectal cancer: colibactin makes its mark | journal=Nature Reviews Gastroenterology & Hepatology | volume=17 | issue=6 | pages=317–318 | year=2020| doi = 10.1038/s41575-020-0303-y | pmid=32317778| s2cid=216033220 }}{{cite journal | vauthors=Zhou T, Hirayama Y, Watanabe K | title=Isolation of New Colibactin Metabolites from Wild-Type Escherichia coli and In Situ Trapping of a Mature Colibactin Derivative | journal=Journal of the American Chemical Society | volume=143 | issue=14 | pages=5526–5533 | year=2021 | doi = 10.1021/jacs.1c01495 | pmid=33787233| s2cid=232431632 }}{{cite journal | vauthors=Helmink BA, Khan M, Wargo JA| title=The microbiome, cancer, and cancer therapy | journal=Nature Medicine | volume=25 | issue=3 | pages=377–388| year=2019 | doi = 10.1038/s41591-019-0377-7 | pmid=30842679| s2cid=71145949 }}{{cite journal | vauthors=Wernke KM, Xue M, Herzon SB | title=Structure and bioactivity of colibactin | journal=Bioorganic & Medicinal Chemistry Letters | volume=30 | issue=15 | pages=127280 | year=2020 | doi = 10.1016/j.bmcl.2020.127280 | pmc=7309967 | pmid=32527463}} especially in early-onset colorectal cancers.{{cite journal |last1=Díaz-Gay |first1=Marcos |last2=dos Santos |first2=Wellington |last3=Moody |first3=Sarah |last4=Kazachkova |first4=Mariya |last5=Abbasi |first5=Ammal |last6=Steele |first6=Christopher D. |last7=Vangara |first7=Raviteja |last8=Senkin |first8=Sergey |last9=Wang |first9=Jingwei |last10=Fitzgerald |first10=Stephen |last11=Bergstrom |first11=Erik N. |last12=Khandekar |first12=Azhar |last13=Otlu |first13=Burçak |last14=Abedi-Ardekani |first14=Behnoush |last15=de Carvalho |first15=Ana Carolina |last16=Cattiaux |first16=Thomas |last17=Penha |first17=Ricardo Cortez Cardoso |last18=Gaborieau |first18=Valérie |last19=Chopard |first19=Priscilia |last20=Carreira |first20=Christine |last21=Cheema |first21=Saamin |last22=Latimer |first22=Calli |last23=Teague |first23=Jon W. |last24=Mukeriya |first24=Anush |last25=Zaridze |first25=David |last26=Cox |first26=Riley |last27=Albert |first27=Monique |last28=Phouthavongsy |first28=Larry |last29=Gallinger |first29=Steven |last30=Malekzadeh |first30=Reza |last31=Niavarani |first31=Ahmadreza |last32=Miladinov |first32=Marko |last33=Erić |first33=Katarina |last34=Milosavljevic |first34=Sasa |last35=Sangrajrang |first35=Suleeporn |last36=Curado |first36=Maria Paula |last37=Aguiar |first37=Samuel |last38=Reis |first38=Rui Manuel |last39=Reis |first39=Monise Tadin |last40=Romagnolo |first40=Luis Gustavo |last41=Guimarães |first41=Denise Peixoto |last42=Holcatova |first42=Ivana |last43=Kalvach |first43=Jaroslav |last44=Vaccaro |first44=Carlos Alberto |last45=Piñero |first45=Tamara Alejandra |last46=Świątkowska |first46=Beata |last47=Lissowska |first47=Jolanta |last48=Roszkowska-Purska |first48=Katarzyna |last49=Huertas-Salgado |first49=Antonio |last50=Shibata |first50=Tatsuhiro |last51=Shiba |first51=Satoshi |last52=Sangkhathat |first52=Surasak |last53=Chitapanarux |first53=Taned |last54=Roshandel |first54=Gholamreza |last55=Ashton-Prolla |first55=Patricia |last56=Damin |first56=Daniel C. |last57=de Oliveira |first57=Francine Hehn |last58=Humphreys |first58=Laura |last59=Lawley |first59=Trevor D. |last60=Perdomo |first60=Sandra |last61=Stratton |first61=Michael R. |last62=Brennan |first62=Paul |last63=Alexandrov |first63=Ludmil B. |title=Geographic and age variations in mutational processes in colorectal cancer |journal=Nature |date=23 April 2025 |doi=10.1038/s41586-025-09025-8 |access-date=23 April 2025 |url=https://www.nature.com/articles/s41586-025-09025-8 |pmid=40267983}} Colibactin is a polyketide peptide that can form interstrand crosslinks in DNA. Colibactin is only produced by bacterial strains containing a polyketide synthase genomic island (pks) or clb biosynthetic gene cluster. About 20% of humans in high-income countries are colonized with E. coli that harbor the pks island.{{cite journal |vauthors=Balskus EP |title=Colibactin: understanding an elusive gut bacterial genotoxin |journal=Natural Product Reports |volume=32 |issue=11 |pages=1534–40 |year=2015 |pmid=26390983 |doi=10.1039/c5np00091b }}{{cite journal |vauthors=Mäklin T, Taira A, Arredondo-Alonso S, Shao Y, Stratton MR, Lawley TD, Aaltonen LA, Corander J |title=Geographical variation in the incidence of colorectal cancer and urinary tract cancer is associated with population exposure to colibactin-producing Escherichia coli |journal=The Lancet Microbe |year=2024 |pmid=39644909 |doi=10.1016/j.lanmic.2024.101015 }}
Colibactin forms DNA inter-strand cross-links by alkylation of adenine moieties on opposing DNA strands. It induces lytic development in certain bacteria that contain prophages.{{Cite journal |last1=Silpe |first1=Justin E. |last2=Wong |first2=Joel W. H. |last3=Owen |first3=Siân V. |last4=Baym |first4=Michael |last5=Balskus |first5=Emily P. |date=2022-02-23 |title=The bacterial toxin colibactin triggers prophage induction |journal=Nature |volume=603 |issue=7900 |language=en |pages=315–320 |doi=10.1038/s41586-022-04444-3|pmid=35197633 |pmc=8907063 |bibcode=2022Natur.603..315S |issn=1476-4687}} Colibactin has been previously demonstrated to have a characteristic mutational signature.{{Cite journal |last1=Pleguezuelos-Manzano |first1=Cayetano |last2=Puschhof |first2=Jens |last3=Rosendahl Huber |first3=Axel |last4=van Hoeck |first4=Arne |last5=Wood |first5=Henry M. |last6=Nomburg |first6=Jason |last7=Gurjao |first7=Carino |last8=Manders |first8=Freek |last9=Dalmasso |first9=Guillaume |last10=Stege |first10=Paul B. |last11=Paganelli |first11=Fernanda L. |last12=Geurts |first12=Maarten H. |last13=Beumer |first13=Joep |last14=Mizutani |first14=Tomohiro |last15=Miao |first15=Yi |date=April 2020 |title=Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli |journal=Nature |language=en |volume=580 |issue=7802 |pages=269–273 |doi=10.1038/s41586-020-2080-8 |pmid=32106218 |pmc=8142898 |issn=1476-4687}} The same mutational signature was discovered in several cohorts of colon cancer patients, and in smaller numbers of patients with urogenital and head and neck cancers. Colibactin exposure has been further linked to a proportion of APC driver indels.