In this study, we devised a novel method to create heterologous producers of lethal antibiotics against host bacteria. Heterologous producers cannot be created when antibiotics are toxic to host bacteria. To overcome this challenge, we developed a novel method involving construction of a combinatorial library with various promoters and screening based on the production. To realize this, we utilized Combi-OGAB (natorial rdered ene ssembly in ), which technology can effectively construct diverse combinatorial library and accelerate screening procedures. and Gramicidin S were selected as the host bacterium and the targeted antibiotic, respectively. The screened producer from Combi-OGAB screening cycles achieved >30-fold productivity over the lethal level. These results suggest that our strategy has the potential to maximize the phenotypic resistance of host bacteria to create heterologous lethal antibiotic producers.
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| http://dx.doi.org/10.1021/acsomega.3c08240 | DOI Listing |
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