Structure elucidation of colibactin and its DNA cross-links

Mengzhao Xue, Chung Sub Kim, Alan Healy, Kevin M. Wernke, Zhixun Wang, Madeline C. Frischling, Emilee E. Shine, Weiwei Wang, Seth B. Herzon, Jason M. Crawford

Research output: Contribution to journalArticle

Abstract

Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, studying the physiological effects of colibactin-producing bacteria in the human gut has been difficult. We used a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin. Our structural assignment accounts for all known biosynthetic and cell biology data and suggests roles for the final unaccounted enzymes in the colibactin gene cluster.

Original languageEnglish (US)
Article numberaax2685
JournalScience
Volume365
Issue number6457
DOIs
StatePublished - Sep 6 2019

Fingerprint

DNA
Isotope Labeling
Bacteria
Multigene Family
Tandem Mass Spectrometry
Cell Biology
colibactin
Colorectal Neoplasms
Escherichia coli
Enzymes

ASJC Scopus subject areas

  • General

Cite this

Xue, M., Kim, C. S., Healy, A., Wernke, K. M., Wang, Z., Frischling, M. C., ... Crawford, J. M. (2019). Structure elucidation of colibactin and its DNA cross-links. Science, 365(6457), [aax2685]. https://doi.org/10.1126/science.aax2685

Structure elucidation of colibactin and its DNA cross-links. / Xue, Mengzhao; Kim, Chung Sub; Healy, Alan; Wernke, Kevin M.; Wang, Zhixun; Frischling, Madeline C.; Shine, Emilee E.; Wang, Weiwei; Herzon, Seth B.; Crawford, Jason M.

In: Science, Vol. 365, No. 6457, aax2685, 06.09.2019.

Research output: Contribution to journalArticle

Xue, M, Kim, CS, Healy, A, Wernke, KM, Wang, Z, Frischling, MC, Shine, EE, Wang, W, Herzon, SB & Crawford, JM 2019, 'Structure elucidation of colibactin and its DNA cross-links', Science, vol. 365, no. 6457, aax2685. https://doi.org/10.1126/science.aax2685
Xue M, Kim CS, Healy A, Wernke KM, Wang Z, Frischling MC et al. Structure elucidation of colibactin and its DNA cross-links. Science. 2019 Sep 6;365(6457). aax2685. https://doi.org/10.1126/science.aax2685
Xue, Mengzhao ; Kim, Chung Sub ; Healy, Alan ; Wernke, Kevin M. ; Wang, Zhixun ; Frischling, Madeline C. ; Shine, Emilee E. ; Wang, Weiwei ; Herzon, Seth B. ; Crawford, Jason M. / Structure elucidation of colibactin and its DNA cross-links. In: Science. 2019 ; Vol. 365, No. 6457.
@article{772c7264baa24df7a54554a0c618a48f,
title = "Structure elucidation of colibactin and its DNA cross-links",
abstract = "Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, studying the physiological effects of colibactin-producing bacteria in the human gut has been difficult. We used a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin. Our structural assignment accounts for all known biosynthetic and cell biology data and suggests roles for the final unaccounted enzymes in the colibactin gene cluster.",
author = "Mengzhao Xue and Kim, {Chung Sub} and Alan Healy and Wernke, {Kevin M.} and Zhixun Wang and Frischling, {Madeline C.} and Shine, {Emilee E.} and Weiwei Wang and Herzon, {Seth B.} and Crawford, {Jason M.}",
year = "2019",
month = "9",
day = "6",
doi = "10.1126/science.aax2685",
language = "English (US)",
volume = "365",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6457",

}

TY - JOUR

T1 - Structure elucidation of colibactin and its DNA cross-links

AU - Xue, Mengzhao

AU - Kim, Chung Sub

AU - Healy, Alan

AU - Wernke, Kevin M.

AU - Wang, Zhixun

AU - Frischling, Madeline C.

AU - Shine, Emilee E.

AU - Wang, Weiwei

AU - Herzon, Seth B.

AU - Crawford, Jason M.

PY - 2019/9/6

Y1 - 2019/9/6

N2 - Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, studying the physiological effects of colibactin-producing bacteria in the human gut has been difficult. We used a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin. Our structural assignment accounts for all known biosynthetic and cell biology data and suggests roles for the final unaccounted enzymes in the colibactin gene cluster.

AB - Colibactin is a complex secondary metabolite produced by some genotoxic gut Escherichia coli strains. The presence of colibactin-producing bacteria correlates with the frequency and severity of colorectal cancer in humans. However, because colibactin has not been isolated or structurally characterized, studying the physiological effects of colibactin-producing bacteria in the human gut has been difficult. We used a combination of genetics, isotope labeling, tandem mass spectrometry, and chemical synthesis to deduce the structure of colibactin. Our structural assignment accounts for all known biosynthetic and cell biology data and suggests roles for the final unaccounted enzymes in the colibactin gene cluster.

UR - http://www.scopus.com/inward/record.url?scp=85071785588&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071785588&partnerID=8YFLogxK

U2 - 10.1126/science.aax2685

DO - 10.1126/science.aax2685

M3 - Article

C2 - 31395743

AN - SCOPUS:85071785588

VL - 365

JO - Science

JF - Science

SN - 0036-8075

IS - 6457

M1 - aax2685

ER -