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

Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR‐Cas9 Activation
Title:
Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR‐Cas9 Activation
Other Titles:
ChemBioChem
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Publication Date:
25 May 2018
Citation:
Y. H. Lim, F. T. Wong, W. L. Yeo, K. C. Ching, Y. W. Lim, E. Heng, S. Chen, D.-J. Tsai, T.-L. Lauderdale, K.-S. Shia, Y. S. Ho, S. Hoon, E. L. Ang, M. M. Zhang, H. Zhao, ChemBioChem 2018, 19, 1716.
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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Funding Info:
Funded by the NRF BTDA grant (NRF2013-THE001-094, M.M.Z., Y.H.L., F.T.W., E.L.A.) and the A*STAR Visiting Investigator Program (H.Z.)
Description:
This is the peer reviewed version of the following article: Y. H. Lim, F. T. Wong, W. L. Yeo, K. C. Ching, Y. W. Lim, E. Heng, S. Chen, D.-J. Tsai, T.-L. Lauderdale, K.-S. Shia, Y. S. Ho, S. Hoon, E. L. Ang, M. M. Zhang, H. Zhao, ChemBioChem 2018, 19, 1716., which has been published in final form at https://doi.org/10.1002/cbic.201800266. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
ISSN:
1439-4227
1439-7633
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