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Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR-Cas9 Activation
- Source :
- Chembiochem : a European journal of chemical biology.
- Publication Year :
- 2018
-
Abstract
- Silent biosynthetic gene clusters represent a potentially rich source of new bioactive compounds. We report the discovery, characterization, and biosynthesis of a novel doubly glycosylated 24-membered polyene macrolactam from a silent biosynthetic gene cluster in Streptomyces roseosporus by using the CRISPR-Cas9 gene cluster activation strategy. Structural characterization of this polyketide, named auroramycin, revealed a rare isobutyrylmalonyl extender unit and a unique pair of amino sugars. Relative and absolute stereochemistry were determined by using a combination of spectroscopic analyses, chemical derivatization, and computational analysis. The activated gene cluster for auroramycin production was also verified by transcriptional analyses and gene deletions. Finally, auroramycin exhibited potent anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity towards clinical drug-resistant isolates.
- Subjects :
- 0301 basic medicine
Glycosylation
Streptomyces roseosporus
biology
Organic Chemistry
biology.organism_classification
Polyene
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Polyketide
030104 developmental biology
chemistry
Biosynthesis
Gene cluster
Molecular Medicine
CRISPR
Molecular Biology
Gene
Subjects
Details
- ISSN :
- 14397633
- Database :
- OpenAIRE
- Journal :
- Chembiochem : a European journal of chemical biology
- Accession number :
- edsair.doi.dedup.....836bc733103f2960b1e44be166a73a9f