基于细胞碳-氮-氧需求的补料批发酵策略促进杆菌肽合成  

Feeding batch fermentation strategy based on cellular demands of carbon-nitrogen-oxygen promotes bacitracin synthesis

作　　者：杨华[1] 宋昭 戴航 陈雄[1] 李欣[1] 陈守文[2] 蔡冬波 李俊辉 王志[1] YANG Hua;SONG Zhao;DAI Hang;CHEN Xiong;LI Xin;CHEN Shouwen;CAI Dongbo;LI Junhui;WANG Zhi(Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Hubei KeyLaboratory of Industrial Microbiology, Hubei University ofTechnology, Wuhan 430068,China;State Key Laboratory of Biocatalysis and Enzyme Engineering (HubeiUniversity), Wuhan 430062, China;Lifecome Biochemistry Co., LTD, Pucheng 353400, China)

机构地区：[1]发酵工程教育部重点实验室,湖北省工业发酵协同创新中心,湖北省工业微生物重点实验室,湖北工业大学,湖北武汉430068 [2]省部共建生物催化与酶工程国家重点实验室(湖北大学),湖北武汉430062 [3]绿康生化股份有限公司,福建浦城353400

出　　处：《食品与发酵工业》2019年第15期30-36,共7页Food and Fermentation Industries

基　　金：省部共建生物催化与酶工程国家重点实验室开放课题(SKLBEE2018005)

摘　　要：为了提高杆菌肽补料发酵的效率,在50 L罐水平研究了pH耦合、间歇-罐压控制和间歇-溶氧(dissolved oxygen, DO)耦合等补料策略对杆菌肽合成的影响。pH耦合策略的杆菌肽效价为1 006 U/mL,但存在对数中后期因pH低于设定值而无法补入葡萄糖的问题。间歇-罐压控制策略的效价(1118 U/mL)比pH耦合策略提高了11%,但也存在发酵后期补糖量与DO不匹配的问题。间歇-DO耦合策略克服了以上缺陷,糖对杆菌肽的转化率( Y P/S )比间歇-罐压控制策略提高了22.7%。基于间歇-DO耦合补料策略并于24 h二次补入氮源后,其平均杆菌肽合成速率达到了40.67 U/(mL·h),杆菌肽效价峰值达到了1220 U/mL。建立了基于细胞需求的综合碳-氮-氧因素的补料策略,为工业化补料发酵生产杆菌肽提供了重要参考。In order to enhance the efficiency of bacitracin fed-batch fermentation, effects of pH coupling, intermittent feeding-tank pressure control, intermittent-dissolved oxygen (DO) coupling and other feeding strategies on bacitracin synthesis were investigated in a 50 L fermenter. The amount of bacitracin produced by pH coupling strategy was1 006 U/mL. However, in middle and late stages of logarithmic growth, glucose could not be filled in due to pH below the set value. Although bacitracin produced by intermittent feeding- tank pressure control strategy was11% higher than that of pH coupling strategy, it also had a problem of sugar-DO mismatched at late fermentation stage. The intermittent-DO coupling strategy overcame the above drawbacks, the conversion rate of sugar to bacitracin ( Y P/S ) increased by22.7% compared with that of intermittent feeding- tank pressure control strategy. Based on intermittent-DO coupling feeding strategy and secondary nitrogen source feeding at24 h, the average bacitracin synthesis rate reached 40.67 U/(mL·h), and the peak value of bacitracin production reached1220 U/mL. Therefore, a feeding strategy based on comprehensive carbon-nitrogen-oxygen factor of cell demand is established, which provides an important reference for industrialized fed-batch fermentation to produce bacitracin.

关 键 词：地衣芽孢杆菌 杆菌肽 补料分批发酵 

分 类 号：TQ920.6[轻工技术与工程—发酵工程]