Carlson Ross, Srienc Friedrich
Department of Chemical Engineering and Materials Science, and BioTechnology Institute, University of Minnesota, 240 Gortner Laboratory, 1479 Gortner Ave, St Paul, Minnesota 55108, USA.
Biotechnol Bioeng. 2004 Apr 20;86(2):149-62. doi: 10.1002/bit.20044.
We have previously shown that the metabolism for most efficient cell growth can be realized by a combination of two types of elementary modes. One mode produces biomass while the second mode generates only energy. The identity of the four most efficient biomass and energy pathway pairs changes, depending on the degree of oxygen limitation. The identification of such pathway pairs for different growth conditions offers a pathway-based explanation of maintenance energy generation. For a given growth rate, experimental aerobic glucose consumption rates can be used to estimate the contribution of each pathway type to the overall metabolic flux pattern. All metabolic fluxes are then completely determined by the stoichiometries of involved pathways defining all nutrient consumption and metabolite secretion rates. We present here equations that permit computation of network fluxes on the basis of unique pathways for the case of optimal, glucose-limited Escherichia coli growth under varying levels of oxygen stress. Predicted glucose and oxygen uptake rates and some metabolite secretion rates are in remarkable agreement with experimental observations supporting the validity of the presented approach. The entire most efficient, steady-state, metabolic rate structure is explicitly defined by the developed equations without need for additional computer simulations. The approach should be generally useful for analyzing and interpreting genomic data by predicting concise, pathway-based metabolic rate structures.
我们之前已经表明，通过两种基本模式的组合可以实现最有效的细胞生长代谢。一种模式产生生物质，而第二种模式仅产生能量。四种最有效的生物质和能量途径对的身份会根据氧气限制程度而变化。确定不同生长条件下的此类途径对为维持能量产生提供了基于途径的解释。对于给定的生长速率，实验性好氧葡萄糖消耗速率可用于估计每种途径类型对整体代谢通量模式的贡献。然后，所有代谢通量完全由定义所有营养物消耗和代谢物分泌速率的相关途径的化学计量决定。我们在此提出一些方程，这些方程允许在不同氧气胁迫水平下，针对最佳、葡萄糖受限的大肠杆菌生长情况，基于独特途径计算网络通量。预测的葡萄糖和氧气摄取速率以及一些代谢物分泌速率与实验观察结果显著一致，支持了所提出方法的有效性。所开发的方程明确地定义了整个最有效的稳态代谢速率结构，无需额外的计算机模拟。该方法通过预测简洁的、基于途径的代谢速率结构，对于分析和解释基因组数据通常应该是有用的。
