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Collinone, a new recombinant angular polyketide antibiotic made by an engineered Streptomyces strain
R Martin1, O Sterner, M A Alvarez
1ETH-Zürich, Institute of Biotechnology, Switzerland.
The Journal of Antibiotics
|May 25, 2001
Summary
Researchers cloned DNA fragments to discover new metabolites. One metabolite, collinone, showed antibacterial activity against resistant bacteria, offering potential for new drug development.
Area of Science:
- Microbiology
- Natural Product Chemistry
- Synthetic Biology
Background:
- The rubromycin polyketide synthase gene cluster is crucial for producing secondary metabolites.
- Streptomyces species are known producers of diverse bioactive compounds, including antibiotics.
Purpose of the Study:
- To identify novel metabolites by expressing rubromycin gene cluster fragments in a heterologous host.
- To characterize the structure and bioactivity of a newly discovered metabolite, collinone.
Main Methods:
- Cloning and functional expression of large chromosomal DNA fragments encoding parts of the rubromycin polyketide synthase gene cluster in *S. coelicolor* CH999.
- Isolation and purification of collinone for spectroscopic structure determination.
- Biological screening assays to evaluate antibacterial, antifungal, and antiviral activities.
Main Results:
- Expression of cloned DNA fragments yielded novel metabolites not found in *S. collinus*.
- Collinone, a hexacyclic compound with an unusual anthracenetetrone moiety, was isolated and characterized.
- Collinone exhibited antibacterial activity against vancomycin-resistant enterococci but lacked significant antifungal or antiviral effects.
Conclusions:
- Collinone represents a novel angucyclin(on)e-like compound with potential therapeutic applications.
- The identified gene cluster and metabolite provide a foundation for developing new bioactive compounds through further genetic engineering.