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Microb Cell Fact ; 19(1): 71, 2020 Mar 19.
Article in English | MEDLINE | ID: mdl-32192516

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.


Subject(s)
Antifungal Agents/isolation & purification , Macrolides/isolation & purification , Streptomyces/genetics , Antifungal Agents/metabolism , Cloning, Molecular , Macrolides/metabolism , Multigene Family , Streptomyces/metabolism
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