Production enhancement of the glycopeptide antibiotic A40926 produced by an engineered N. gerenzanensis lcu1

Abstract

Objective To enhance the production of A40926 by implementing a strategy of the combination of genetically engineered strain construction and medium optimization. Results The engineered strain of Nonomuraea gerenzanensis presented an increment of 30.6 percent in A40926 production compared with that of the parent strain. Subsequently, an assembling medium, which was defined as M9 medium and mainly comprised glucose, maltodextrin, soybean meal, peptone, L-valine, and other inorganic salts, was determined as the optimal medium among the tested nine media. The optimum concentration of medium components was glucose 10 g/l, maltodextrin 37.9 g/l, soybean meal 34.5 g/l, peptone 30.0 g/l, and L-valine 4.3 g/l, respectively. The optimized medium was verified experimentally, and A40926 yield increased significantly from 257 mg/l to 332 mg/l, as compared to the non-optimized medium. The strategy brought a significant increase of A40926 yield by 65.2 percent. Conclusions The engineered mutant with the genetic attributes of the co-expression of the dbv3 and dbv20 genes and the deletion of the dbv23 gene could obviously enhance the production of A40926. In addition, the optimization of medium was an effective and essential tool for the improvement of the secondary metabolites in Actinomyces.