Goh, F., Zhang, M.M., Lim, T.R. et al. Identification and engineering of 32 membered antifungal macrolactone notonesomycins. Microb Cell Fact 19, 71 (2020). https://doi.org/10.1186/s12934-020-01328-x
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.
This research is supported by core funding from the Bioinformatics Institute, ARES. WLY, EH, MMZ, FTW are supported by National Research Foundation, Singapore [NRF2013-THE001-094].