Researchers unlock cancer-causing mechanism of E. coli toxin with synthetic biology approach

Now, a research team led by Prof. Qian Peiyuan, Chair Professor of HKUST’s Department of Ocean Science and Division of Life Science, have unearthed the missing link using a novel biosynthetic method. The team not only succeeded in cloning the colibactin gene cluster, but also found a way to mass produce the genes for testing and validation. After repeated assays of various sets of colibactin precursors, the team eventually identified colibactin-645 as the culprit of the DNA double-strand breaks, and uncovered colibactin metabolite’s biosynthetic pathway as well as its mechanism of causing DNA damage.

Prof. Qian said, “Although a few colibactin metabolites have been reported to damage DNA via DNA crosslinking activity, the genotoxic colibactin that possesses DNA double-strands directly is yet-to-be-identified. Our research has confirmed colibactin-645 exerts direct DNA double-strand breaks, that unearthed the missing link that correlates colibactin to its health effects on human beings.”

LI Zhongrui, a researcher of the team, said the restructuring of colibactin’s molecular scaffold provides a model for designing and synthesizing potent DNA cleaving agents — such as synthetic restriction “enzymes” or chemotherapeutic agents.

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