Identification and engineering of 32 membered antifungal macrolactone notonesomycins
| Autor: | Shawn Hoon, Alexander Lezhava, Fernanda L. Sirota, Sharon Crasta, Frank Eisenhaber, Zann Tan, Choy Eng Nge, Swaine L. Chen, Veronica Ng, Birgit Eisenhaber, Siew Bee Ng, Mingzi M. Zhang, Huibin Zhang, Chung Yan Leong, Kia Ngee Low, Falicia Goh, Fong Tian Wong, Tian Ru Lim, Wan Lin Yeo, Yoganathan Kanagasundaram, Elena Heng |
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| Přispěvatelé: | School of Computer Science and Engineering |
| Rok vydání: | 2020 |
| Předmět: |
Bioengineering [Engineering]
Antifungal Antifungal Agents Stereochemistry medicine.drug_class lcsh:QR1-502 Biosynthetic gene cluster Bioengineering CRISPR–Cas9 Polyketide Applied Microbiology and Biotechnology Streptomyces lcsh:Microbiology Natural product 03 medical and health sciences chemistry.chemical_compound Natural Product Gene cluster medicine Sulfation Cloning Molecular Streptomyces antibiotic regulatory protein 030304 developmental biology 0303 health sciences Strain (chemistry) biology 030306 microbiology Research biology.organism_classification chemistry Multigene Family Macrolides Biotechnology |
| Zdroj: | Microbial Cell Factories Microbial Cell Factories, Vol 19, Iss 1, Pp 1-13 (2020) |
| ISSN: | 1475-2859 |
| DOI: | 10.1186/s12934-020-01328-x |
| Popis: | 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. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version This work was supported by the Agency for Science, Technology and Research (A*STAR), Singapore. WLY, EH, MMZ, FTW are supported by National Research Foundation, Singapore [NRF2013-THE001-094]. |
| Databáze: | OpenAIRE |
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