1. Identification and engineering of 32 membered antifungal macrolactone notonesomycins
- Author
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Falicia Goh, Mingzi M. Zhang, Tian Ru Lim, Kia Ngee Low, Choy Eng Nge, Elena Heng, Wan Lin Yeo, Fernanda L. Sirota, Sharon Crasta, Zann Tan, Veronica Ng, Chung Yan Leong, Huibin Zhang, Alexander Lezhava, Swaine L. Chen, Shawn S. Hoon, Frank Eisenhaber, Birgit Eisenhaber, Yoganathan Kanagasundaram, Fong T. Wong, and Siew Bee Ng
- Subjects
Natural product ,Polyketide ,Biosynthetic gene cluster ,CRISPR–Cas9 ,Sulfation ,Streptomyces antibiotic regulatory protein ,Microbiology ,QR1-502 - Abstract
Abstract Notonesomycin A is a 32-membered bioactive glycosylated macrolactone known to be produced by Streptomyces aminophilus subsp. notonesogenes 647-AV1 and S. aminophilus DSM 40186. In a high throughput antifungal screening campaign, we identified an alternative notonesomycin A producing strain, Streptomyces sp. A793, and its biosynthetic gene cluster. From this strain, we further characterized a new more potent antifungal non-sulfated analogue, named notonesomycin B. Through CRISPR–Cas9 engineering of the biosynthetic gene cluster, we were able to increase the production yield of notonesomycin B by up to 18-fold as well as generate a strain that exclusively produces this analogue.
- Published
- 2020
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