Tetracycline compounds with c8 polysaccharide modification and biosynthetic method and application thereof

By introducing polysaccharide modification at the C8 position of tetracycline compounds and synthesizing new compounds using recombinant strain technology, the problem of resistance to drug-resistant bacteria in existing tetracycline antibiotics has been solved. Significant inhibitory activity against Staphylococcus aureus and Enterococcus faecalis has been achieved, providing a new method for structural modification and biosynthesis.

CN122404446APending Publication Date: 2026-07-17INST OF MICROBIOLOGY CHINESE ACAD OF SCI
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
INST OF MICROBIOLOGY CHINESE ACAD OF SCI
Filing Date
2026-03-26
Publication Date
2026-07-17

AI Technical Summary

Technical Problem

Existing tetracycline antibiotics have limitations in structural modification, making them difficult to effectively combat drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis, and there is a lack of new biosynthetic methods.

Method used

By introducing polysaccharide modification at the C8 position of tetracycline compounds, the ech gene cluster of *Streptomyces oryzae* was expressed in *Streptomyces micranthum* using recombinant strain technology, and new tetracycline compounds with C8 polysaccharide modification were synthesized. The compounds were then purified using resin adsorption and chromatography techniques.

Benefits of technology

The synthesized tetracycline compounds modified with C8 polysaccharide groups showed significant inhibitory activity against drug-resistant bacteria such as Staphylococcus aureus and Enterococcus faecalis, providing new structural modification groups and alternative compounds, and laying the foundation for the innovative development of tetracycline skeleton antibiotics.

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Abstract

This invention belongs to the field of synthetic biology and discloses tetracycline compounds modified with a polysaccharide group at the C8 position, their biosynthetic methods, and applications. The tetracycline compounds with a polysaccharide group modification at the C8 position provided by this invention have a novel structure; the trisaccharide and hexasaccharide groups present at the C8 position are not found in known tetracycline natural products or tetracycline skeleton antibiotics. The biosynthetic method involves using a polysaccharide group derived from *Streptomyces rubrum*. ech Gene clusters, in which mis This invention expresses the gene cluster in the *Streptomyces micranthum* host, fully utilizing the different biosynthetic enzymes contained in two similar but different tetracycline natural product biosynthetic gene clusters to synthesize novel compounds that neither host bacterium can synthesize. These compounds exhibit significant inhibitory activity against *Staphylococcus aureus*, *Enterococcus faecalis*, and *Enterococcus faecium*. This invention provides new candidate compounds for the innovative development of tetracycline-based antibacterial drugs and is of great significance to the development of microbial drug resources.
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