基于计算机模拟的大肠杆菌产琥珀酸最优代谢途径分析.pdfVIP

I022 基于计算机模拟的大肠杆菌产琥珀酸 最优代谢途径分析 王庆昭 赵学明 （天津大学化工学院生物化学工程系, 天津300072 ） 要 本文以大肠杆菌为研究对象，系统研究了其琥珀酸的代谢途径。通过选取一些最相关的 代谢反应重建了基于计算机模拟的大肠杆菌基本代谢网络，并建立了计量学模型。通过线性规划 软件LINDO 计算，估计了在各种条件下最优的代谢产生琥珀酸的途径以及理论最大产率。按照 本文的代谢模型，在有氧条件下的琥珀酸最高产率可以达到 0.65 g 琥珀酸/克葡萄糖；而在厌氧 条件下的最大产率为1.12 g 琥珀酸/克葡萄糖。通过分析发现PTS 途径对琥珀酸的产量有较大的 影响而丙酮酸羧化酶和苹果酸酶的影响则较小。这和以往的研究文献一致。根据我们的研究数据， 在JB=0.1 时的最优代谢路径不再是只通过TCA 循环的还原臂进行而涉及到乙醛酸循环的部 通 量。这时的理论最大产率为1.05 g 琥珀酸/g 葡萄糖。 关键词 琥珀酸 代谢工程 计算机模拟 途径优化 中图分类号 TQ 933 文献标识码 A IN SILICO OPTIMAL METABOLIC PATHWAY ANALYSIS OF Escherichia coli FOR SUCCINIC ACID PRODUCTION WANG Qingzhao and ZHAO Xueming (Depa rtment of Biochemical Engineering , School of Chemical Engineering Technology, Tianji n University, Tianji n, 300072) Abstract In this paper, we use the E.coli as the example, studied systematically the succinic acid production pathway. By selecting the fundamental reactions, we reconstructed the E.coli fundamental network and established in silico metabolic model. Through the LINDO liner program, we estimated the maximum in silico yield of succinic acid and the optimal flux distribution. According to this model, the maximum succinic acid is 0.65g/g glucose in aerobic situation. However it is 1.12g/g glucose in anaerobic situation. We also find that PTS pathway is essential for succinic acid production, but the PYR carboxylase and Malic enzyme is not. That conforms to the past documented findings. Finally, based on our results, the optimal pathway is not only through the TCA reductive arm, but also with the glyoxylate shunt. The maximum yield in theory is 1.05g/g glucose. Keywords succinic acid，metabolic engineering ，in silico simulation，pathway optimum 引 言 代谢工程通过运用重组DNA 技术和其他分子生物学技术引入、敲除