Metabolic Flux Analysis and Principal Nodes Identification for Daptomycin Production Improvement by Streptomyces roseosporus
Metabolic Flux Analysis and Principal Nodes Identification for Daptomycin Production Improvement by Streptomyces roseosporus
复制标题
玫瑰孢链霉菌提高达托霉素产量的代谢通量分析和主节点鉴定
DOI：
10.1007/s12010-011-9390-0
复制
发表时间：
2011-12-01
影响因子：
3
通讯作者：
Chen, Yunlin
中科院分区：
文献类型：
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作者：
Huang, Di;Jia, Xiaoqiang;Chen, Yunlin
本研究建立了玫瑰孢链霉菌LC-54-20生产达托霉素的代谢网络。除了达托霉素和生物质生产外，还评价了整个分批发酵过程中细胞外代谢物的分析。代谢通量分布是基于化学计量反应以及胞外代谢物通量。 通过控制不同的pH值，本文还介绍了各种胞外代谢产物的生产率。通量分布变化表明，葡萄糖6-磷酸、3-磷酸甘油酸、磷酸烯醇丙酮酸、丙酮酸和草酰乙酸的分支点可显著影响达托霉素的生产。这五种主要代谢产物被证明是灵活的节点，并可能成为进一步提高达托霉素产量的潜在瓶颈。在分批发酵过程中添加不同浓度的前体物质，可提高达托霉素的产量和产率。
In the present work, a comprehensive metabolic network of Streptomyces roseosporus LC-54-20 was proposed for daptomycin production. The analysis of extracellular metabolites throughout the batch fermentation was evaluated in addition to daptomycin and biomass production. Metabolic flux distributions were based on stoichiometrical reaction as well as the extracellular metabolites fluxes. Through manipulating different pH values, the production rates of various extracellular metabolites were also presented in this paper. Flux distribution variations revealed that the daptomycin production could be significantly influenced by the branch points of glucose 6-phosphate, 3-phosphoglycerate, phosphoenolpyruvate, pyruvate, and oxaloacetate. The five principal metabolites were certified as the flexible nodes and could form potential bottlenecks for a further enhancement of daptomycin production. Furthermore, various concentrations of the five precursors were added into the batch fermentation and led to the enhancement of daptomycin concentration and production rate.