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

Fermentation

Adriana Bava¹  Fabrizio Beltrametti¹  Elisa Binda²  Francesca Berini²  Flavia Marinelli² 

[1] BioC-CheM Solutions Srl, Via R. Lepetit 34, 21040 Gerenzano, Italy;Department of Biotechnology and Life Sciences, University of Insubria, Via J.H. Dunant 3, 21100 Varese, Italy;

关键词: dalbavancin;    A40926;    Nonomuraea gerenzanensis;    glycopeptide antibiotics;    antibiotic resistance;    strain improvement;   

DOI  :  10.3390/fermentation7030140

来源: DOAJ

【 摘 要 】

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

【 授权许可】

Unknown