Notonesomycin A

Fermentation of Streptomyces aminophilus subsp. notonesogenes 647-AV1 produced a mixture of antifungal antibiotics. Notonesomycin A, the main component has been characterized as a new macrolide antibiotic containing a sulfate group, a malonate moiety, two deoxysugars and a 1,3,4-trisubstituted benzene system in the molecule. It was active against some fungi and Gram-positive bacteria in vitro and effective against the sheath blight disease of rice plant in a green house test.

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.