| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Microbial Cell Factories, Vol 19, Iss 1, Pp 1-11 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1475-2859 |
| DOI: |
10.1186/s12934-019-1274-y |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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