國家衛生研究院 NHRI:Item 3990099045/12462
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    题名: Biosynthetic engineering of the antifungal, anti-MRSA auroramycin
    作者: Yeo, WL;Heng, E;Tan, LL;Lim, YW;Ching, KC;Tsai, DJ;Jhang, YW;Lauderdale, TL;Shia, KS;Zhao, H;Ang, EL;Zhang, MM;Lim, YH;Wong, FT
    贡献者: National Institute of Infectious Diseases and Vaccinology;Institute of Biotechnology and Pharmaceutical Research
    摘要: Using an established CRISPR-Cas mediated genome editing technique for streptomycetes, we explored the combinatorial biosynthesis potential of the auroramycin biosynthetic gene cluster in Streptomyces roseosporous. Auroramycin is a potent anti-MRSA polyene macrolactam. In addition, auroramycin has antifungal activities, which is unique among structurally similar polyene macrolactams, such as incednine and silvalactam. In this work, we employed different engineering strategies to target glycosylation and acylation biosynthetic machineries within its recently elucidated biosynthetic pathway. Auroramycin analogs with variations in C-, N- methylation, hydroxylation and extender units incorporation were produced and characterized. By comparing the bioactivity profiles of five of these analogs, we determined that unique disaccharide motif of auroramycin is essential for its antimicrobial bioactivity. We further demonstrated that C-methylation of the 3, 5-epi-lemonose unit, which is unique among structurally similar polyene macrolactams, is key to its antifungal activity.
    日期: 2020-01-06
    關聯: Microbial Cell Factories. 2020 Jan 6;19:Article number 3.
    Link to: http://dx.doi.org/10.1186/s12934-019-1274-y
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1475-2859&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000513860000002
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85077568848
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