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Biosynthetic Genes for the Tetrodecamycin Antibiotics
Tomas Gverzdys1, Justin R Nodwell2
1Department of Biochemistry, University of Toronto, Toronto, Canada.
Journal of Bacteriology
|May 4, 2016
Summary
Researchers identified the biosynthetic genes for 13-deoxytetrodecamycin, a tetrodecamycin antibiotic. This discovery sheds light on the tetronate ring formation and reveals new related molecules with potential biological activity.
Area of Science:
- Microbiology
- Molecular Biology
- Natural Product Chemistry
Background:
- Tetrodecamycins are a subgroup of tetronate antibiotics with unknown biosynthesis and mechanisms of action.
- 13-deoxytetrodecamycin is a recently described member of this antibiotic family.
Purpose of the Study:
- To identify the biosynthetic gene cluster for 13-deoxytetrodecamycin.
- To investigate the biosynthesis of tetrodecamycin family antibiotics.
- To discover novel molecules within this pathway.
Main Methods:
- Genome sequencing of Streptomyces sp. strain WAC04657.
- Identification and comparison of homologous gene clusters in related organisms.
- Genetic manipulation of the identified gene cluster.
Main Results:
- The biosynthetic genes (ted genes) for 13-deoxytetrodecamycin were identified.
- Related gene clusters were found in Streptomyces atroolivaceus, Streptomyces globisporus, and Streptomyces sp. strain LaPpAH-202.
- Genetic manipulation confirmed the role of ted genes and revealed the production of tetrodecamycin, dihydrotetrodecamycin, and a novel molecule W5.9.
Conclusions:
- The ted gene cluster is responsible for 13-deoxytetrodecamycin biosynthesis.
- The tetrodecamycin pathway produces a family of related molecules.
- These molecules may exert their bioactivity through covalent modification of targets.
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