Fermentation Process Optimization Of High Natamycin Production Strain

Natamycin,also known as pimaricin,is a polyene macrolide antibiotic which can inhibits growth of yeasts and fungi effectively.Attribute to its broad spectrum of activity,lack of development of resistance,low water solubility and non-toxic,natamycin is widely used as an antifungal agent in the food industry and in pharmacotherapy for topical treatment.However,its long fermentation cycle and low production efficiency lead to high cost which has limited its application on large scale.Therefore,it has significance to improve natamycin yield and reduce cost by fermentation process optimization of high natamycin production strain.Combined with relative paper and information,some selective optimization was chose to improve natamycin yield of Streptomyces natalensis,such as soybean oil addition or instead of starch.All the optimization adopted single factor and orthogonal design to improve carbon source(oil optimization),nitrogen source,ratio of carbon source and nitrogen source and the content of calcium carbonate.Based on these,effect of other factors such as phosphate,inorganic nitrogen source,metal ion and ferrocyanide on S natalensis were investigated.The results indicated that the most suitable carbon,nitrogen,inorganic nitrogen sources,inorganic salts for S.natalensis were soybean oil,mixture of soybean meal,rape seed cake and peptone,ammonium sulfate and magnesium sulfate respectively.Soybean oil had the most effective program to get high yield natamycin taking all these factors consideration.When soybean oil was used as carbon source,the titer reached 13.78 g/L with 55.6%improved.And the titer peaked at 23.03 g/L when the fermentation cycle extended to 11 days.So this method can enhance natamycin biosynthesis and reduce cost of natamycin effectively.The impacts of soybean oil on S.natalensis fermentation were analyzed initially and found that soybean oil can provide precursors for natamycin biosynthesis not just act as carbon source.Not only medium optimization,cultivation conditions optimization such as inoculum time,inoculum size,volume,initial pH,shear force and temperature control also play an important part in S.natalensis fermentation.The results indicated that initial pH and dissolved oxygen had a big impact on natamycin yield.Improving dissolved oxygen by reducing volume and increasing shear force,and lowering inoculum size and initial pH can increase natamycin yield obviously.Besides that,feeding is another method to improve natamycin production.Firstly,glucose was added to medium but it cannot improve natamycin yield whenever and however much it was added.Secondly,various short-chain fatty acids and lower alcohols were added to the medium and propanol was found to be the most effective factor.Under the optimal condition of propanol addition,the maximal natamycin production titer reached 10.38 g/L,which was 17.0%higher than that of the control.Lastly,propanol’s function on S.natalensis fermentation was analyzed by extracellular organic acids,amino acids and AcCoA between propanol added medium and control.Propanol is proved to be regulating metabolite note and pools of precursor.