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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 the treatment of type II diabetes.According to the established genome-scale metabolic network model iYLW1028, the fermentation of acarbose produced by Actinoplane s sp. SE50 / 110 was simulated and performed according to the simulation results Fermentation and optimization.The results showed that nicotinic acid increased the production rate of acarbose by 8.2% according to model iYLW1028, 20 kinds of amino acids had a positive effect on acarbose accumulation, histidine increased 58.7%, and the proton emission was robust Sex analysis showed that acarbose was more sensitive to pH than cell growth and neutral pH favored acarbose. Oxygen robust analysis showed that relatively low dissolved oxygen levels (0.1917 m mol g ~ (-1) h ~ (-1)) was beneficial to the accumulation of acarbose.In the wet experiment, nicotinic acid (5 mg / L) increased acarbose production by 53.5%; glutamic acid, cysteine, lysine , Glutamine and asparagine respectively increased the production of acarbose by 29.6%, 26.5%, 26.3%, 11.8% and 9.2%, respectively. Controlling the neutral pH of fermentation compared with control pH and acidic pH resulted in acarbose production Increased by 7% and 15%, respectively. Acarbose had the highest yield (1.11 g / L) at 0.5 vvm ventilation.The results of this study showed that the combination of metabolic model Guidance optimization method for the fermentation of fermentation products have some reference.