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.
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.
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.)
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.