Fermentation Process Optimization And Suppressed Foam Promoter Research Of The FK520Production By An Industrial Strain

Foam is one of the major problems in the industrial fermentation of FK520,which will lower the working volume of the bioreactor, suppress the production ofFK520, cause contamination and other fermentation problems. In recent years, thefermentation research on ascomycin is in the primary stage and researches toward thefermentation process optimization are just started. There is little related reportsfocused on the foam during the industrial fermentation of FK520. Therefore, in thisresearch, we will start to learn the fermentation process from analyzing the productionof FK520, then learn to control the fermentation foam caused by the foam contributor.First, we optimized the fermentation process to improve FK520production in a7.5-L bioreactor (NBS BioFlow1110, America). The optimized aeration volume is1.5vvm; while the optimized stirring process are: keep DO at50%to shorten the lagphase during0-24h; keep DO at30%to meet the oxygen demand of cells and avoidthe cell damages caused by the stirring during the early log phase in24-48h; keep DOat10%to avoid the serious damages caused by vigorous stirring during the middleand late log phase in48-72h; keep the stirring speed at400rpm to maintain theconsistence of the fermentation broth during the stationary phase since72-168h.According to the HPLC analysis, FK520production reached its maximum value375mg/L at168h, increased40.08%compared with that under the original fermentationconditions.Second, HPLC analysis（Agilent2000, America） and high-resolution bio-sensor(SBA-40C, China) were used to analyze the fermentation broth. In7.5-L bioreactor,the concentration of organic acid foam promoter was changed from160mg/L to325mg/L, increased by103.1%; foam height changed from0.76cm to4.37cm, increasedby475%during72-120h; while during120-168h, as the concentration of foampromoter maintained within the range of280-325mg/L, the foam height maintainedin the range of4.37-5.07cm, quite stable.Third, to reveal the specific content of organic acid foam promoter, HPLCanalysis was conducted through which acetate was proved to be one foam promoter.We noted that when there is0.05%(mass ration) acetate in the fermentation broth,foam height was changed from1.55cm to6.45cm, increased by314%.Fourth, to suppress the biosynthesis of acetate,40g/L glycerol-water dilutionwas added with speed of0.2ml/min into fermentation broth at0-72h to replace20 g/L starch, to finally lower the biomass then lower the production speed of acetate;30%pure oxygen and70%air were mixed to feed the fermentation broth from48-96h tofurther suppress the biosynthesis of acetate;0.01mL/min organic silicon antifoamwas added into the fermentation broth since72-144h to further control theacetate-type foam. After the optimization, the maximum acetate concentrationdropped from325mg/L to162mg/L, decreased by50.8%; maximum foam heightdropped from5.07cm to3.42cm, decreased by32.5%; maximum FK520concentration changed from375mg/L to421mg/L, increased by12%.