Milbemycin strain with high-yield and its application

A method for producing milbemycin by fermentation of Streptomyces hygroscopicus var. aureolacrimosus HZMRYB-5, specifically comprising:

• inoculating a seed liquid of a strain HZMRYB-5 into a fermentation culture medium at an inoculation amount of 5-20% by volume fraction, wherein the strain HZMRYB-5 is Streptomyces hygroscopicus var. aureolacrimosus HZMRYB-5 with a deposit number of CCTCC:
• M 20231540, the culture temperature is 28.0-30.0° C. during whole fermentation process;
• the tank pressure is 0.02-0.06 MPa;
• ventilation is controlled at 0.2-1.0 vvm at 0-24 h, gradually increased to 1.0-1.8 vvm, and then gradually decreased to 1.0-1.2 vvm before completion of fermentation;
• the rotation speed is gradually increased to 250-500 rpm at 0-48 h, and gradually decreased to 100-200 rpm in a later stage of fermentation;
• natural pH;
• the dissolved oxygen (DO) value is controlled to be equal to or greater than 50%;
• and the fermentation period is 300-400 h;
• when the total sugar content is 5.0-8.0%, a supplement culture medium is supplemented in 1-3 times every day according to 1-4% of the volume of the fermentation liquid;
• wherein the supplement culture medium comprises:
• all materials in the formulation of the fermentation culture medium with a double concentration;
• and a w/v composition of the fermentation culture medium is:
• 10-30% of sucrose, 0.5-3% of skim milk powder, 2-4% of soybean meal powder, 1-4% of cottonseed cake meal, 0.1-0.5% of potassium nitrate, 0.1-0.5% of dipotassium hydrogen phosphate, 0.1-1.0% of zeolite powder, 0.001-0.01% of sodium molybdate, 0.01-0.1% of magnesium sulfate heptahydrate, 0.01-0.05% of ferrous sulfate, 0.01-0.1% of sodium acetate, 0.1-1% of methyl oleate, 0.1-1% of liquid paraffin and the balance of water, and has a pH value of 7.2.

A method for producing milbemycin by fermentation, wherein a seed liquid is obtained by mixed culture of a strain MI-W1-2017001 and a strain HZMRYB-5;

• and the strain HZMRYB-5 is Streptomyces hygroscopicus var. aureolacrimosus HZMRYB-5, with a deposit number of CCTCC:
• M 20231540;
• and the strain MI-W1-2017001 is specifically Streptomyces hygroscopicus var. aureolacrimosus MI-W1-2017001, with a deposit number of CCTCC NO:
• M 2021292;
• wherein the seed liquid is inoculated into a fermentation culture medium at an inoculation amount of 5-20%;
• the culture temperature is 28.0-30.0° C. in the whole process;
• the tank pressure is 0.02-0.06 Mpa;
• ventilation is controlled at 0.2-1.0 vvm at 0-24 h, gradually increased to 1.0-1.8 vvm, and then gradually decreased to 1.0-1.2 vvm at 12-144 h before completion of fermentation;
• the rotation speed is gradually increased to 250-500 rpm at 0-48 h, and gradually decreased to 100-200 rpm at 20-120 h before completion of fermentation;
• natural pH;
• the DO value is controlled to be equal to or greater than 50%;
• and the fermentation period is 300-400 h;
• when the total sugar content is about 5.0-8.0%, a supplement culture medium is supplemented in 1-3 times every day according to 1-4% of the volume of the fermentation liquid;
• the supplement culture medium comprises:
• all materials in a formulation of the fermentation culture medium with a double concentration;
• a w/v composition of the fermentation culture medium is:
• 20% of sucrose, 2% of skim milk powder, 2% of soybean meal powder, 2% of cottonseed cake meal, 0.1% of potassium nitrate, 0.2% of dipotassium hydrogen phosphate, 0.4% of zeolite powder, 0.005% of sodium molybdate, 0.05% of magnesium sulfate heptahydrate, 0.01% of ferrous sulfate, 0.04% of sodium acetate, 0.1% of methyl oleate, 0.5% of liquid paraffin and the balance of water, and has a pH value of 7.2;
• and the seed liquid is obtained by mixed culture of a strain MI-W1-2017001 and a strain HZMRYB-5, and during preparation of the seed liquid, the strain MI-W1-2017001 and the strain HZMRYB-5 are inoculated at a ratio of 1:2.