Biosynthetic engineering of the antifungal, anti-MRSA auroramycin

Wan Lin Yeo, Elena Heng, Lee Ling Tan, Yi Wee Lim, Kuan Chieh Ching, De Juin Tsai, Yi Wun Jhang, Tsai Ling Lauderdale, Kak Shan Shia, Huimin Zhao, Ee Lui Ang, Mingzi M. Zhang, Yee Hwee Lim, Fong T. Wong

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number3
JournalMicrobial cell factories
Volume19
Issue number1
DOIs
StatePublished - Jan 6 2020

Keywords

  • Combinatorial biosynthesis
  • Polyene macrolactam
  • Streptomyces

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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  • Cite this

    Yeo, W. L., Heng, E., Tan, L. L., Lim, Y. W., Ching, K. C., Tsai, D. J., Jhang, Y. W., Lauderdale, T. L., Shia, K. S., Zhao, H., Ang, E. L., Zhang, M. M., Lim, Y. H., & Wong, F. T. (2020). Biosynthetic engineering of the antifungal, anti-MRSA auroramycin. Microbial cell factories, 19(1), [3]. https://doi.org/10.1186/s12934-019-1274-y