Study On The Optimization Of Lipstatin Fermentation

Lipstatin is a secondary metabolite of Streptomyces toxytricini and it is aneffective gastrointestinal pancreatic lipase inhibitor. Orlistat, the hydrogenationproduct of Lipstatin, is an important drug for the prevention and treatment of diseasesassociated with obesity, it has only slight side effect on human health and it has noacting on the central system, and it has become the main anti-obesity drug in themarket in the past decade.In this work, the optimization of lipstatin fermentation medium was studiedbased on the previous research work in this laboratory. Pursuant to the results ofsingle factor experiment of our laboratory, we carried out orthogonal experiments offermentation medium. The optimum fermentation culture medium formula is: linoleicacid3.0%, soybean flour6.0%, glycerin2.5%, lecithin1.0%. The titer is increased by17.1%. Then, the inorganic salt in fermentation medium was also investigated, whenK₂HPO₄0.09%, MgSO₄0.01%, the lipstatin titer can be increased by2.3%. Besides,the defoaming agent was also studied, the bubbles can be better controlled.On the basis of optimized culture medium, we carried out orthogonal experimentin10L fermentation tank to optimize fermentation technological conditions andobtained the best process conditions:27℃, pH7.0, seed age30h, inoculationsige9%.We also found that when the medium loading capacity is7.0L, stirring speed is260rpm, aeration rate is0.8vvm, the lipstatin titer can be effectively improved. Thepoikilothermal fermentation was also studied. After vaccination, maintainingtemperature at27℃, after36h fermentation,adjust temperature to25℃, comparedwith thermostatic cultivation, lipstatin titer was increased by3.5%.With the optimal fermentation medium and conditions, linoleic acid/caprylic acid,L-leucine and soybean oil fed-batch process were studied in the fermentation process,the lipstatin fermentation titer was greatly improved by19.5%under optimal feedingtechnology. After optimization of the fermentation process, the lipstatin titer was greatlyimproved. The optimization of the lipstatin fermentation process has importantguiding significance to industrial production.