Biosynthetic engineering of the antifungal, anti-MRSA auroramycin [article]

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 (+2 others)
2019 bioRxiv   pre-print
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 roseoporous. Auroramycin is a potent anti-MRSA polyene macrolactam. In addition, it also displays 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
more » ... to target glycosylation and acylation biosynthetic machineries within its recently elucidated biosynthetic pathway. Six auroramycin analogs with variations in C-, N- methylation, hydroxylation and extender units incorporation were produced and characterized. By comparing the bioactivity profiles 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.
doi:10.1101/829812 fatcat:sylcl4ai6vecnj3tl2ussa7mvq