Identification and engineering of 32 membered antifungal macrolactone notonesomycins

Author:

Goh Falicia,Zhang Mingzi M.,Lim Tian Ru,Low Kia Ngee,Nge Choy Eng,Heng Elena,Yeo Wan Lin,Sirota Fernanda L.,Crasta Sharon,Tan Zann,Ng Veronica,Leong Chung Yan,Zhang Huibin,Lezhava Alexander,Chen Swaine L.,Hoon Shawn S.,Eisenhaber Frank,Eisenhaber Birgit,Kanagasundaram Yoganathan,Wong Fong T.,Ng Siew Bee

Abstract

AbstractNotonesomycin 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.

Funder

National Research Foundation Singapore

Publisher

Springer Science and Business Media LLC

Subject

Applied Microbiology and Biotechnology,Bioengineering,Biotechnology

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