The application discloses a
spiramycin fermentation method based on
nitrogen source regulation, and relates to the technical field of
spiramycin fermentation. The application improves the
spiramycin fermentation titer and reduces the generation levels of impurities D and F without changing the production strain, introducing complex genetic modification and large equipment modification, by adjusting the ratio of the available
inorganic nitrogen source and the composite organic
nitrogen source in the initial culture medium, and optimizing the composition of the organic
nitrogen source in the feeding stage. The application can solve the problems in the existing mature fermentation process, such as the limited
titer improvement space, the possible influence of the slow-release organic
nitrogen source such as
soybean meal on
impurity F in the feeding stage, the mismatch between the nitrogen
metabolism rhythm and the
secondary metabolism start caused by the too fast use of the available
ammonium salt, and the high
impurity D level in the late fermentation stage. The application also verifies the action mechanism of the
nitrogen source regulation process by the changes of the total
sugar, amino nitrogen and related
biosynthesis gene expression in the fermentation process, and provides a basis for subsequent process amplification and
quality control.