Abstract: The biosynthesis of spiramycin (SPM) by streptomyces spiramyceticus sp. 799 was regulated by carbon and nitrogen catabolite repression as well as end products feedback repression. Mutants resistant to glucose, ammonium ion and SPM were obtained by subjecting the spores to mutagens, UV or DES, and selecting by analogue-resistant technique. The mutants thus obtained produced more SPM than the parent strains. The improvement of the productivity and properties of releasing from catabolite repression and end product feedback regulation of the mutants were also confirmed 15y resting cell culture system.