Tumor-targeting drug-producing engineering strain, construction method and application thereof

By constructing an engineered strain of Escherichia coli Nissle 1917, introducing the romidesin biosynthesis gene cluster, and utilizing promoter regulation, the problem of weak antitumor activity of Escherichia coli Nissle 1917 was solved, enabling in situ production of romidesin in tumors and significantly improving the antitumor effect.

CN119685232BActive Publication Date: 2026-06-02SHANDONG UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
SHANDONG UNIV
Filing Date
2024-12-23
Publication Date
2026-06-02

AI Technical Summary

Technical Problem

In the existing technology, Escherichia coli Nissle 1917 has weak antitumor activity, and there are few studies on its biosynthesis of small molecule drugs. The application of romidesin biosynthesis in tumor-targeting bacteria has not been reported.

Method used

An engineered strain of *Escherichia coli* Nissle 1917 containing the romididisin biosynthesis pathway was constructed. Exogenous romididisin biosynthesis gene clusters were introduced through Red/ET homologous recombination technology and regulated using the BAD, Tet, and Pfnrs promoters to construct an engineered strain for tumor-targeted drug production.

Benefits of technology

The study achieved in situ production of romidesin in tumor-bearing small animals, significantly enhancing its antitumor activity and effectively inhibiting the growth of hematologic malignancies and solid tumors.

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Abstract

The present application belongs to the field of microbial genetic engineering technology, and particularly relates to tumor-targeting drug-producing engineering strains and a construction method and application thereof. The present application discloses a series of tumor-targeting drug-producing engineering strains, which can produce the anticancer drug romidepsin in situ in a tumor, can heterologously express romidepsin, and can produce romidepsin in situ in a tumor of a tumor-bearing small animal and has the activity of inhibiting tumor growth. That is, the present application provides a series of Escherichia coli Nissle 1917 recombinant strains, which are expected to become an anticancer live bacterial drug and will be applied to the clinic in the future, and therefore have good practical application value.
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