July 7, 2019  |  

Auroramycin, a potent antibiotic from Streptomyces roseosporus by CRISPR-Cas9 activation.

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

Silent biosynthetic gene clusters represent a potentially rich source for 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 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 aminosugars. Relative and absolute stereochemistry were determined 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.© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Journal: Chembiochem
DOI: 10.1002/cbic.201800266
Year: 2018

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