論文

国際誌
2021年4月14日

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
  • Tao Zhou
  • ,
  • Yuichiro Hirayama
  • ,
  • Yuta Tsunematsu
  • ,
  • Nanami Suzuki
  • ,
  • Seiji Tanaka
  • ,
  • Nahoko Uchiyama
  • ,
  • Yukihiro Goda
  • ,
  • Yuko Yoshikawa
  • ,
  • Yuji Iwashita
  • ,
  • Michio Sato
  • ,
  • Noriyuki Miyoshi
  • ,
  • Michihiro Mutoh
  • ,
  • Hideki Ishikawa
  • ,
  • Haruhiko Sugimura
  • ,
  • Keiji Wakabayashi
  • ,
  • Kenji Watanabe

143
14
開始ページ
5526
終了ページ
5533
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1021/jacs.1c01495

Colibactin is a polyketide-nonribosomal peptide hybrid secondary metabolite that can form interstrand cross-links in double-stranded DNA. Colibactin-producing Escherichia coli has also been linked to colorectal oncogenesis. Thus, there is a strong interest in understanding the role colibactin may play in oncogenesis. Here, using the high-colibactin-producing wild-type E. coli strain we isolated from a clinical sample with the activity-based fluorescent probe we developed earlier, we were able to identify colibactin 770, which was recently identified and proposed as the complete form of colibactin, along with colibactin 788, 406, 416, 420, and 430 derived from colibactin 770 through structural rearrangements and solvolysis. Furthermore, we were able to trap the degrading mature colibactin species by converting the diketone moiety into quinoxaline in situ in the crude culture extract to form colibactin 860 at milligram scale. This allowed us to determine the stereochemically complex structure of the rearranged form of an intact colibactin, colibactin 788, in detail. Furthermore, our study suggested that we were capturing only a few percent of the actual colibactin produced by the microbe, providing a crude quantitative insight into the inherent instability of this compound. Through the structural assignment of colibactins and their degradative products by the combination of LC-HRMS and NMR spectroscopies, we were able to elucidate further the fate of inherently unstable colibactin, which could help acquire a more complete picture of colibactin metabolism and identify key DNA adducts and biomarkers for diagnosing colorectal cancer.

リンク情報
DOI
https://doi.org/10.1021/jacs.1c01495
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33787233
ID情報
  • DOI : 10.1021/jacs.1c01495
  • PubMed ID : 33787233

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