Isolation of New Colibactin Metabolites from Wild-Type Escherichia coli and In Situ Trapping of a Mature Colibactin Derivative
| العنوان: | Isolation of New Colibactin Metabolites from Wild-Type Escherichia coli and In Situ Trapping of a Mature Colibactin Derivative |
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| المؤلفون: | Yuji Iwashita, Nahoko Uchiyama, Noriyuki Miyoshi, Seiji Tanaka, Michio Sato, Hideki Ishikawa, Haruhiko Sugimura, Tao Zhou, Yuichiro Hirayama, Kenji Watanabe, Nanami Suzuki, Yukihiro Goda, Yuta Tsunematsu, Michihiro Mutoh, Yuko Yoshikawa, Keiji Wakabayashi |
| المصدر: | Journal of the American Chemical Society. 143:5526-5533 |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | In situ, chemistry.chemical_classification, Chemistry, Wild type, Peptide, General Chemistry, Secondary metabolite, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, Catalysis, 0104 chemical sciences, chemistry.chemical_compound, Colloid and Surface Chemistry, Colibactin, medicine, Escherichia coli, Derivative (chemistry), DNA, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1520-5126 0002-7863 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::1d885120780f7226479d0b1513dd8004 https://doi.org/10.1021/jacs.1c01495 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........1d885120780f7226479d0b1513dd8004 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15205126 00027863 |
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