Optimization Of Bioprocess For Echinocandin B Production

Anidulafungin is a semisynthetic echinocandin used as a novel antifungal drug.Owing to its good curative effect,low toxicity and good resistance for other antifungal drugs,anidulafungin is called as “trump card” among the antifungal drugs.Echinocandin B(ECB),as the precursor of anidulafungin,is fermentationed by Aspergillus nidulans.In this work,the A.nidulans ZJB09223 strain was selected for ECB production mutagenized by our lab.the culture conditions further optimization was used to further improve ECB production based on medium optimization by our research group,and the use of temperature-shift and fed-batch fermentation combine strategy,and a scale-up culture in 50 L fermentor,the results are as follows:The effects of temperature-shift culture combine mannitol fed to the ECB fermentation.The results showed that by kinetics analysis at different temperatures,a temperature-shift culture strategy was to establish: the first 6 days using 30 ? culture,promote the rapid growth of cell and reach secondary metabolism,the culture temperature was adjusted to 25 ? in the seventh day,the cell maintained higher synthesis efficiency,the production of ECB has increased from 1453 mg/L up to 1720 mg/L,which was 18% higher than control.Base on temperature-shift culture strategy,fed-batch cultivation have been investigated and the initial mannitol concetration is 48.5 g/L,then the rest of mannitol was added by three times(3th,6th,9th),the production of ECB has increased to 2047 mg/L from 1720 mg/L,which was 20% higher than control.In 50 L fementation,It is favorable that the dissolved oxygen above 30% and pH of the fermentation broth is maintained at 6-7,the production of ECB has increased from 756 mg/L to 1772 mg/L,production has increased by 1.34 times.