While high-colibactin-producing Escherichia coli is thought to be associated with colorectal oncogenesis, this study is complicated part due to an inability to isolate colibactin adequately. Here, we created fluorescent probes activated by ClbP, the colibactin-maturing peptidase, to identify high-colibactin-producing strains. Our probe served as a valuable clinical diagnostic tool that allowed simple high-throughput diagnostic screening of clinical samples. Furthermore, the probe also allowed identification of high-colibactin producers that would help advance our understanding of colibactin biosynthesis.
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Advancing the Biosynthetic and Chemical Understanding of the Carcinogenic Risk Factor Colibactin and Its Producers.
Biochemistry
December 2022
Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
Recent studies have shown that often carries a biosynthetic gene cluster termed either the island or the cluster that allows the production of a genotoxic polyketide-nonribosomal peptide hybrid secondary metabolite called colibactin. While the gene cluster is not always expressed, when the strain that resides in the colon produces the genotoxin, it is suspected to become a risk factor for colorectal cancer. Therefore, there is great interest in devising a simple method for the detection of colibactin-producing strains and understanding the detailed mechanism of how colibactin can induce oncogenesis, to develop convenient early screening methods and possible preventive treatments against colorectal cancer.
View Article and Find Full Text PDFIsolation of New Colibactin Metabolites from Wild-Type and Trapping of a Mature Colibactin Derivative.
J Am Chem Soc
April 2021
Adenoprevent Co., Ltd., Shizuoka 422-8526, Japan.
Colibactin is a polyketide-nonribosomal peptide hybrid secondary metabolite that can form interstrand cross-links in double-stranded DNA. Colibactin-producing has also been linked to colorectal oncogenesis. Thus, there is a strong interest in understanding the role colibactin may play in oncogenesis.
View Article and Find Full Text PDFActivity-Based Probe for Screening of High-Colibactin Producers from Clinical Samples.
Org Lett
June 2019
Department of Pharmaceutical Sciences , University of Shizuoka, Shizuoka 422-8526 , Japan.
While high-colibactin-producing Escherichia coli is thought to be associated with colorectal oncogenesis, this study is complicated part due to an inability to isolate colibactin adequately. Here, we created fluorescent probes activated by ClbP, the colibactin-maturing peptidase, to identify high-colibactin-producing strains. Our probe served as a valuable clinical diagnostic tool that allowed simple high-throughput diagnostic screening of clinical samples.
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