Skip to Content
Merck
  • Identification and engineering of 32 membered antifungal macrolactone notonesomycins.

Identification and engineering of 32 membered antifungal macrolactone notonesomycins.

Microbial cell factories (2020-03-21)
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, Siew Bee Ng
PMID32192516
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.