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[1]王雅丽,刘立明,史仲平.基于Actinoplanes sp. SE50/110基因组规模代谢模型优化阿卡波糖生产[J].应用与环境生物学报,2015,21(06):1065-1070.[doi:10.3724/SP.J.1145.2015.04040]
 WANG Yali,LIU Liming,SHI Zhongping.Fermentation optimization for acarbose production based on the genome-scale metabolic model of Actinoplanes sp. SE50/110[J].Chinese Journal of Applied & Environmental Biology,2015,21(06):1065-1070.[doi:10.3724/SP.J.1145.2015.04040]
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基于Actinoplanes sp. SE50/110基因组规模代谢模型优化阿卡波糖生产()
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《应用与环境生物学报》[ISSN:1006-687X/CN:51-1482/Q]

卷:
21卷
期数:
2015年06期
页码:
1065-1070
栏目:
研究论文
出版日期:
2015-12-25

文章信息/Info

Title:
Fermentation optimization for acarbose production based on the genome-scale metabolic model of Actinoplanes sp. SE50/110
作者:
王雅丽 刘立明 史仲平
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
Author(s):
WANG Yali LIU Liming SHI Zhongping
1State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; 2The Key Laboratory of Industrial Biotechnology of the Ministry of Education, Jiangnan University, Wuxi 214122, China
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
Keywords:
Actinoplanes sp. SE50/110 genome-scale metabolic model acarbose fermentation optimization
分类号:
Q815
DOI:
10.3724/SP.J.1145.2015.04040
文献标志码:
A
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iYLW1028,对Actinoplanes 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 mmol 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.
Abstract:
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 iYLW1028 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 increased acarbose producing rate by 8.2%. Addition of 20 amino acids promoted production of acarbose; 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/gDCW/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 improving acarbose production as well as production of other related products.

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备注/Memo

备注/Memo:
国家自然科学基金项目(21422602)资助 Supported by the National Natural Science Foundation of China (21422602)
更新日期/Last Update: 2016-01-05