Organ transplantation faces the problem of immune rejection while giving patients a second life. Rapamycin is a new type of macrolide antibiotic, and it is also a widely used clinical drug for the treatment of immune rejection, which can greatly improve the survival rate of transplanted organs after surgery. But this medicine is low productivity and it is also expensive. Our project intends to construct an engineered strain by means of genetic engineering, mainly by knocking out the two-component system encoding gene M271_14685/M271_14690 in Streptomyces rapamycinicus, optimizing the metabolic regulatory network of rapamycin biosynthesis, and improving the fermentation yield of the rapamycin, which will bring greater value to clinical treatment and help patients which take organ transplantations.