Study On Fermentation Conditions Of Nosiheptide

Nosiheptide is a sulfur-containing peptide veterinary antibiotics product of fermentation by Streptomyces actuosus dedicated the new environmentally friendly green antibiotic for a high efficiency and low toxicity of livestock growth promoters. However, the yield of nosiheptide at present is very low, so the application of nosiheptide is limited severely duo to the high cost of production. Therefore, the process of nosiheptide fermentation depth research and is very great significance. In order to improve the fermentation level of nosiheptide36, strains preserved in laboratory fermentation process optimization, Streptomyces actuosus slant culture conditions, shake flask fermentation conditions and medium, and fermentation kinetics preliminary study.The slant medium cultivation conditions of Streptomyces actuosus were investigated to explore optimum process of fermentation synthesis of nosiheptide in shake flask. Single factors experiment and orthogonal design were used to optimize culture conditions of the slant medium. The highest production of nosiheptide (936mg/L) was obtained under the following slant medium cultivation conditions:initial pH7.8, culture temperature37℃, incubation time3d and cold store time0-3w, which was increased by13.8%compared to the original process.The paper studied fermentation conditions for Streptomyces actuosus36which synthesized nosiheptide in shake flask. The results showed most of seed age, inoculums level, initial pH, dissolved oxygen and temperature on nosiheptide yield, cell dry weight, sugar utilization, dry weight yield and bacterial sugar consumption rate based on cell firstly increases and then decreases within the experimental range. The highest production of nosiheptide (1194mg/L) was obtained under the following cultivation conditions:seed age40h, inoculums level5%, initial pH value6.5, dissolved oxygen8%and28℃. The yield of nosiheptide increased by29.3%compared to the original process. With studying Streptomyces actuosus in shake flasks control pH seed initial pH6.5, we found that dry weight of the bacteria was the highest and the bacteria were the most stout. Using uniform test, the optimization strategies of pH control were medium initial of pH5.5, initial pH5.5fermentation medium and fermentation process control pH6.8, was1118mg/L and6.1%higher than the original process. According to nosiheptide biosynthesis component, the precursors was investigated the effects on the yield of nosiheptide. The serine was used to value the promoting effect on biosynthesis nosiheptide, and better than serine, threonine, tryptophan, glutamic acid, semi-ammoniaacid, alanine and methionine. The suitable precursors of serine were best effect of time and concentration for48h and0.3mg/L, respectively. Under this condition, the yield of nosiheptide was up to1033mg/L, and a17.2%was increased with comparing to the precursor was not added.Using uniform test, the mixed carbon source recipe were obtained by the fermentation medium in shake flasks:liquefied starch of8%, dextrin of1.5%, glucose of2%. The yield of nosiheptide was up to1451mg/L. The results were55%higher than the original process. Optimized program was used to10L fermenter, which can promote nosiheptide bacterial breeding, improve concentration and vitality of the mycelium, shorten the time of the primary metabolism, extend the corresponding secondary metabolites and improve the yield of nosiheptide.Using10L fermenter, the Logistic Equation was used to describe Streptomyces actuosus growth. The Luedeking-Piret equation was used to describe nosiheptide generation. The like Luedekin-Piret equation was used to describe sugar consumption. The model was able to reflect the batch fermentation nosiheptide process.