基于Actinoplanes sp.SE50/110基因组规模代谢模型优化阿卡波糖生产  

Fermentation optimization for acarbose production based on the genome-scale metabolic model of Actinoplanes sp. SE50/110

作　　者：王雅丽[1,2] 刘立明[1] 史仲平[2] 

机构地区：[1]江南大学食品科学与技术国家重点实验室,无锡214122 [2]江南大学工业生物技术教育部重点实验室,无锡214122

出　　处：《应用与环境生物学报》2015年第6期1065-1070,共6页Chinese Journal of Applied and Environmental Biology

基　　金：国家自然科学基金项目(21422602)资助~~

摘　　要：阿卡波糖是广泛应用的Ⅱ型糖尿病治疗药物.根据已经建立的基因组规模代谢网络模型i YLW1028,对Act inoplane s sp.SE50/110生产阿卡波糖的发酵进行模拟,并根据模拟结果进行发酵优化.结果显示:根据模型iYLW1028模拟,烟酸使阿卡波糖产生速率提高8.2%;20种氨基酸对阿卡波糖积累有积极作用,组氨酸使其提高58.7%;质子排放鲁棒性分析表明阿卡波糖的产生比细胞生长对pH值更敏感,中性pH利于阿卡波糖产生;氧气鲁棒性分析表明相对低的溶氧水平(0.1917 m mol g^(-1) h^(-1))利于阿卡波糖积累.在湿实验中,烟酸(5 mg/L)使阿卡波糖产量提高了53.5%;谷氨酸、半胱氨酸、赖氨酸、谷氨酰胺和天冬酰胺分别使阿卡波糖产量提高了29.6%、26.5%、26.3%、11.8%和9.2%;控制发酵中性pH比不控pH和酸性pH使阿卡波糖产量提高了7%和15%;0.5 vvm的通气量时阿卡波糖产量最高(1.11 g/L).本研究结果表明,结合代谢模型指导的优化方法对相关发酵产品的发酵优化具有一定的借鉴作用.Acarbose is a widely used drug for Diabetes mellitus type II. The aim of this study was to improve acarbose production based on in silico simulation of genome-scale metabolic model of Actinoplanes sp. SE50/110. Strategies of improving acarbose production were simulated based on model i YLW1028 of Actinoplanes sp. SE50/110, and batch fermentation optimization was conducted based on the in silico simulation. The results showed that addition of nicotinic acid incre ased acarbose producing rate by 8.2%. Addition of 20 amino acids promoted production of acarb ose; especially addition of histidine led to an increase of 58.7% in acarbose producing rate. Acarbose producing rate was more sensitive to pH than cell growth rate was; the acarbose production in the neutral pH（pH 7） was 7% and 15% respectively higher than in the uncontrolled and acid environment（pH 5.5）. Robustness analysis of oxygen indicated that a relatively low dissolved oxygen level（0.1917 mmol/g DCW/h） was good for acarbose production; an aeration rate of 0.5 vvm led to acarbose production of 1.11 g/L, being the maximal among all aerations. In the batch fermentation, nicotinic acid（5 mg/L） increased acarbose production by 53.5%; glutamic acid, cysteine, lysine and glutamine lead to increase of acarbose production by 29.62%, 26.45%, 26.27%, 11.83% and 9.17%, respectively. The results indicated that fermentation optimization based on genome-scale metabolic model of Actinoplanes sp. SE50/110 is helpful for impro ving acarbose production as well as production of other related products.

关 键 词：ACTINOPLANES sp.SE50/110 基因组规模代谢网络模型 阿卡波糖 发酵优化 

分 类 号：TQ464.1[化学工程—制药化工]