Improvement of lincomycin production by mutant selection and metabolic regulation

Lincomycin is a lincosamide antibiotic produced by <i>Streptomyces lincolnensis</i>. Through mutagenesis by ethylmethansulfonate (EMS) and ultraviolet (UV) irradiation repeatedly, M2 was picked out in plate with glutamine and propylproline orderly. In 50-L stirred bioreactor, the production of lincomycin, fermented by M2, was increased to 8136 u/ml under the optimal condition as compared to original strain<i>S. lincolnensis</i> 07-5 (6634 u/ml). Two-dimensional gel electrophoresis (2-D GE) and mass spectrometry (MS) shown LmbG, LmbI and acetohydroxy acid isomeroreductase were remarkably synthesized in M2. The gene <i>lmbG</i> and <i>lmbI</i> are responsible for methylation in the lincomycin biosynthetic cluster, while acetohydroxy acid isomeroreductase contributes to stronger metabolic capability. Finally, we obtained a better strain for industrial production.