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Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR‐Cas9 Activation
Author(s) -
Lim Yee Hwee,
Wong Fong Tian,
Yeo Wan Lin,
Ching Kuan Chieh,
Lim Yi Wee,
Heng Elena,
Chen Shuwen,
Tsai DeJuin,
Lauderdale TsaiLing,
Shia KakShan,
Ho Ying Swan,
Hoon Shawn,
Ang Ee Lui,
Zhang Mingzi M.,
Zhao Huimin
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800266
Subject(s) - gene cluster , polyketide , gene , crispr , polyene , streptomyces , polyketide synthase , biosynthesis , chemistry , biochemistry , biology , derivatization , stereochemistry , computational biology , genetics , bacteria , mass spectrometry , chromatography
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.