Heterogeneous A40926 Self-Resistance Profile in Nonomuraea gerenzanensis Population Informs Strain Improvement

Nonomuraea gerenzanensis ATCC 39727 produces the glycopeptide antibiotic A40926, which is natural precursor of semi-synthetic, last-resort drug dalbavancin. To reduce cost dalbavancin production, it mandatory to improve productivity producing strain. Here, we report that exposure N. wild-type population sub-inhibitory concentrations A40926 led isolation differently resistant phenotypes a diverse was associated. The most (G, grand colonies) represented at least 20% colonies growing on 2 µg/mL A40926. It showed stable phenotype after sub-culturing and homogeneous profile self-resistance in analysis (PAP) experiments. less (P, petit) by slow-growing lower At bioreactor scale, G variant produced twice more than (ca. 400 mg/L versus 200 mg/L, respectively), paving way for rational strain improvement based selection increasingly self-resistant colonies.