A new strategy for dynamic metabolic flux estimation by integrating transient metabolome data into genome-scale metabolic models
A new strategy for dynamic metabolic flux estimation by integrating transient metabolome data into genome-scale metabolic models
复制标题
通过将瞬时代谢组数据整合到基因组规模代谢模型中来估计动态代谢通量的新策略
DOI：
10.1007/s00449-021-02626-3
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发表时间：
2021-08
影响因子：
3.8
通讯作者：
Henk Noorman
中科院分区：
文献类型：
--
作者：
Peng Liu;Ye Hua;Wei Zhang;Tingting Xie;Yingping Zhuang;Jianye Xia;Henk Noorman
代谢通量分析（MFA）是研究微生物细胞生理的有力工具。基于同位素的MFA是研究稳态条件下代谢通量的公认标准。然而，由于缺乏适当的技术，如快速采样和淬火、高成本和费力的执行，它在动态胞外条件下的应用受到限制。在这里，我们提出了一种新的策略，通过将动态代谢物丰度数据纳入基因组尺度代谢模型（GEM）来解决这个问题。首先，为每一种动态变化的代谢物提出了一个虚拟的细胞外池概念，它代表一个“汇”或“源”，并将相应的虚拟反应编码到GEM模型中。然后将动态模型（以微分方程表示）转化为准稳态模型（以线性方程表示），用动态代谢物定量数据约束GEM模型即可轻松求解。为此，采用了常用的线性规划优化算法来估计动态通量。通过同位素稀释质谱（IDMS）方法和高速采样-猝灭获得了动态的高精度代谢物丰度数据，并证明了新提出的策略可以成功地应用于单次和周期性细胞外葡萄糖脉冲制度下的黑曲霉胞内动态通量。在酿酒酵母葡萄糖脉冲响应研究中，验证了新方法在动态通量估计中的适用性。所提出的方法为研究动态条件下的细胞生理学提供了有力的工具，特别是与生物工艺扩大到工业规模的生物反应器相关。
Metabolic flux analysis (MFA) is a powerful tool for studying microbial cell physiology. Isotope-based MFA is the accepted standard for studying metabolic fluxes under steady-state conditions. However, its application under dynamic extracellular conditions is limited due to lack of proper techniques, such as rapid sampling and quenching, high cost and laborious execution. Here, we propose a new strategy to tackle this through incorporating dynamic metabolite abundance data into genome-scale metabolic models (GEM). First, a dummy extracellular pool concept is proposed for each dynamically changing metabolite, which represents a “sink” or “source”, with corresponding dummy reactions coded into the GEM model. The dynamic model (expressed as differential equations) is then transformed into a quasi-steady-state model (expressed as linear equations), which can be easily solved by constraining the GEM model with the dynamic metabolite quantification data. For this, common linear-programming optimization algorithms were utilized to estimate the dynamic fluxes. Dynamic high-accuracy metabolite abundance data were obtained through the Isotope Dilution Mass Spectrometry (IDMS) method and high-speed sampling-quenching, and it was demonstrated that the newly proposed strategy could be successfully applied to obtain intracellular dynamic fluxes ofAspergillus nigerunder regimes of single and periodic extracellular glucose pulses. The applicability of the new method was also tested on dynamic fluxes estimation in a glucose pulse-response study ofSaccharomyces cerevisiae. The proposed method provides a powerful tool to investigate cell physiology under dynamic conditions, especially relevant for bioprocess scale-up to industrial-scale bioreactors.
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影响因子：
4.1
作者：
Suarez-Mendez CA;Sousa A;Heijnen JJ;Wahl A
通讯作者：
Wahl A
影响因子：
2.7
作者：
Brandl, Julian;Andersen, Mikael R.
通讯作者：
Andersen, Mikael R.
影响因子：
3.8
作者：
Wenjun Tang;A. Deshmukh;C. Haringa;Guan Wang;W. V. van Gulik;W. V. van Winden;M. Reuss;J. Heijnen-J.-Heij
通讯作者：
Wenjun Tang;A. Deshmukh;C. Haringa;Guan Wang;W. V. van Gulik;W. V. van Winden;M. Reuss;J. Heijnen-J.-Heij
影响因子：
4.2
作者：
Chang, Liang;Liu, Xinggao;Henson, Michael A.
通讯作者：
Henson, Michael A.
黑曲霉对葡萄糖扰动的动态代谢反应：减少葡糖淀粉酶产生的调节机制的证据
影响因子：
4.1
作者：
Li, Chao;Shu, Wei;Xia, Jianye
通讯作者：
Xia, Jianye