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.

中文翻译：

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鉴定和工程化的32元抗真菌大内酯Notonesomycins

Notonesomycin A是32员具有生物活性的糖基化大内酯，已知由氨基链霉菌亚种生产。notonesogenes 647-AV1和S. aminophilus DSM40186。在高通量抗真菌筛选活动中，我们鉴定了另一种产生notonesomycin A的菌株Streptomyces sp。A793及其生物合成基因簇。从该菌株中，我们进一步鉴定了一种新的更有效的抗真菌非硫酸盐类似物，命名为notonesomycinB。通过生物合成基因簇的CRISPR-Cas9工程，我们能够将notonesomycin B的产量提高18倍。并产生只产生该类似物的菌株。