%0 Journal Article
%T Enhanced porcine interferon-alpha production by Pichia pastoris by methanol/sorbitol co-feeding and energy metabolism shift<br>甲醇/山梨醇共混流加诱导改变毕赤酵母生产猪α干扰素过程的代谢产能途径强化发酵性能
%A Huihui Wang
%A Hu Jin
%A Minjie Gao
%A Keke Dai
%A Shijuan Dong
%A Ruisong Yu
%A Zhen Li
%A Zhongping Shi
%A <br>汪汇慧
%A 金虎
%A 高敏杰
%A 戴科科
%A 董世娟
%A 于瑞嵩
%A 李震
%A 史仲平
%J 生物工程学报
%D 2012
%I 
%X Porcine interferon-alpha (pIFN-alpha) fermentative production by recombinant Pichia pastoris was carried out in a 10-L bioreactor to study its metabolism changes and effects on fermentation under different inducing strategies, by analyzing the change patterns of the corresponding metabolism and energy regeneration. The results show that the specific activities of alcohol oxidase (AOX), formaldehyde dehydrogenase (FLD) and formate dehydrogenase (FDH) largely increased when reducing temperature from 30 degrees C to 20 degrees C under pure methanol induction, leading significant enhancements in methanol metabolism, formaldehyde dissimilatory energy metabolism and pIFN-alpha antiviral activity. The highest pIFN-alpha antiviral activity reached 1.4 x 10(6) IU/mL, which was about 10-folds of that obtained under 30 degrees C induction. Using methanol/sorbitol co-feeding strategy at 30 degrees C, the major energy metabolism energizing pIFN-alpha synthesis shifted from formaldehyde dissimilatory energy metabolism pathway to TCA cycle, formaldehyde dissimilatory pathway was weakened and accumulation of toxic intermediate metabolite-formaldehyde was relieved, and methanol flux distribution towards to pIFN-alpha synthesis was enhanced. Under this condition, the highest pIFN-alpha antiviral activity reached 1.8 x 10(7) IU/mL which was about 100-folds of that obtained under pure methanol induction at 30 degrees C. More important, enhanced pIFN-alpha production with methanol/sorbitol co-feeding strategy could be implemented under mild conditions, which greatly reduced the fermentation costs and improved the entire fermentation performance.
%K Pichia pastoris
%K metabolic analysis
%K methanol
%K sorbitol
%K temperature
%K induction
%K porcine interferon-α<br>毕赤酵母
%K 代谢分析
%K 甲醇
%K 山梨醇
%K 温度
%K 诱导
%K 猪α干扰素
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=90BA3D13E7F3BC869AC96FB3DA594E3FE34FBF7B8BC0E591&jid=A66E90C274451689E69F6F0291467824&aid=399F4AB6A5A1DC872EFCCFDD2EAC0F97&yid=99E9153A83D4CB11&vid=D3E34374A0D77D7F&iid=0B39A22176CE99FB&sid=F260CE035846B3B8&eid=6425DAE0271BB751&journal_id=1000-3061&journal_name=生物工程学报&referenced_num=0&reference_num=0