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Published on: February 26, 2019
Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR-Cas9 Activation
Yee Hwee Lim1, Fong Tian Wong2, Wan Lin Yeo3
1Organic Chemistry, Institute of Chemical and Engineering Sciences (ICES), A*STAR, 8 Biomedical Grove, Neuros #07-01/02/03, Singapore, 138665, Singapore.
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.
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