Primary Study On Improvement Of Lincomycin A Production And Purity In Fermentation Of A Industrial Strain Streptomyces Lincolnensis By Genetic Engineering

Lincomycin and its semi-derivative, clindamycin, are two lincosmide antibiotics widely used in clinic to be active against gram-positive microorganisms. However, the relatively low production of lincomycin A and the presence of the by-product lincomycin B in fermentation broth are challenging to the fermentation industry in China. In this study, we attempted to introduce into a industrial strain S. lincolnensis N9 additional copy of methylation genes orf25 and/or orfl2, regulatory genes orf22 or orf29, or entire gene cluster in lincomycin biosynthesis, aiming at improving lincomycin A production and purity at the fermentation stage. S. lincolnensis N9 was genetically accessible and introduction of exogenous DNA had no apparent impact on lincomycin production. The productions in the mutants LIN-W, LIN-WJ, LIN-Q and LIN-1E8, which carry the recombinant fragments ermE*+orf25, ermE*+orf25+orfl2, ermE*+orf25, ermE*+orf25 as well as the entire lincomycin biosynthetic gene cluster, respectively, were improved by 5.52%,13.75%,6.24% and 17.3%. In addition, the proportion of lincomycin B in fermentation of mutant LIN-WJ was decreased to 8.92%, in comparison to 11.34% present in the original strain S. lincolnensis N9.