Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR-Cas9 Activation

Yee Hwee Lim, Fong Tian Wong, Wan Lin Yeo, Kuan Chieh Ching, Yi Wee Lim, Elena Heng, Shuwen Chen, De Juin Tsai, Tsai Ling Lauderdale, Kak Shan Shia, Ying Swan Ho, Shawn Hoon, Ee Lui Ang, Mingzi M. Zhang, Huimin Zhao

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1716-1719
Number of pages4
JournalChemBioChem
Volume19
Issue number16
DOIs
StatePublished - Aug 16 2018

Keywords

  • biosynthesis
  • genomics
  • glycosylation
  • lactams
  • natural products

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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  • Cite this

    Lim, Y. H., Wong, F. T., Yeo, W. L., Ching, K. C., Lim, Y. W., Heng, E., Chen, S., Tsai, D. J., Lauderdale, T. L., Shia, K. S., Ho, Y. S., Hoon, S., Ang, E. L., Zhang, M. M., & Zhao, H. (2018). Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR-Cas9 Activation. ChemBioChem, 19(16), 1716-1719. https://doi.org/10.1002/cbic.201800266