Limited Mechanistic Link Between the Monod Equation and Methanogen Growth: a Perspective from Metabolic Modeling.
Limited Mechanistic Link Between the Monod Equation and Methanogen Growth: a Perspective from Metabolic Modeling.
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DOI：
10.1128/spectrum.02259-21
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发表时间：
2022-04-27
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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Monod方程作为微生物生长的一般速率定律得到了广泛的应用，但其应用并不总是成功的。通过绘制动力学和化学计量代谢模型和代谢控制分析的框架，这里报道的建模模拟产甲烷微生物的生长动力学，并说明不同的酶和代谢产物控制生长速率到不同程度，其控制峰值在非常低，中间或非常高的底物浓度。相比之下，与一个单一的术语和两个参数，莫诺方程仅约占控制速率决定酶和代谢物在非常高和非常低的底物浓度，但忽略了酶和代谢物的控制是最显着的中间浓度。这些发现支持莫诺方程和产甲烷菌生长之间的有限联系，并统一了关于酶在形成生长动力学中的作用的竞争观点。这些结果还排除了从产甲烷菌代谢网络中机械推导莫诺方程的可能性，并凸显了微生物学中的一个根本挑战：单项表达式可能不足以准确预测微生物生长。莫诺方程已被广泛应用于预测微生物的生长速度，但它的应用并不总是成功的。使用一种新的代谢建模方法，我们模拟了产甲烷菌的生长，并揭示了莫诺方程和产甲烷菌的代谢网络之间的有限的机械联系。具体而言，该方程通过在极低和极高底物浓度下的速率决定代谢物和酶提供了对照的近似值，但其缺失了在中间浓度下其对照最显著的其余酶和代谢物。这些结果支持莫诺方程作为一个有用的近似生长速率，并强调了一个基本的挑战，在微生物动力学：单项速率表达式可能不足以准确预测微生物的生长。
The Monod equation has been widely applied as the general rate law of microbial growth, but its applications are not always successful. By drawing on the frameworks of kinetic and stoichiometric metabolic models and metabolic control analysis, the modeling reported here simulated the growth kinetics of a methanogenic microorganism and illustrated that different enzymes and metabolites control growth rate to various extents and that their controls peak at either very low, intermediate, or very high substrate concentrations. In comparison, with a single term and two parameters, the Monod equation only approximately accounts for the controls of rate-determining enzymes and metabolites at very high and very low substrate concentrations, but neglects the enzymes and metabolites whose controls are most notable at intermediate concentrations. These findings support a limited link between the Monod equation and methanogen growth, and unify the competing views regarding enzyme roles in shaping growth kinetics. The results also preclude a mechanistic derivation of the Monod equation from methanogen metabolic networks and highlight a fundamental challenge in microbiology: single-term expressions may not be sufficient for accurate prediction of microbial growth. IMPORTANCE The Monod equation has been widely applied to predict the rate of microbial growth, but its application is not always successful. Using a novel metabolic modeling approach, we simulated the growth of a methanogen and uncovered a limited mechanistic link between the Monod equation and the methanogen’s metabolic network. Specifically, the equation provides an approximation to the controls by rate-determining metabolites and enzymes at very low and very high substrate concentrations, but it is missing the remaining enzymes and metabolites whose controls are most notable at intermediate concentrations. These results support the Monod equation as a useful approximation of growth rates and highlight a fundamental challenge in microbial kinetics: single-term rate expressions may not be sufficient for accurate prediction of microbial growth.
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DOI：
10.1046/j.1432-1033.2003.03362.x
发表时间：
2003-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
de Poorter, LMI;Geerts, WG;Keltjens, JT
通讯作者：
Keltjens, JT
影响因子：
4.4
作者：
Cronwright, GR;Rohwer, JM;Prior, BA
通讯作者：
Prior, BA
影响因子：
3.9
作者：
Alvarez-Ramirez, Jose;Meraz, M.;Jaime Vernon-Carter, E.
通讯作者：
Jaime Vernon-Carter, E.
影响因子：
3.6
作者：
HEALEY, FP
通讯作者：
HEALEY, FP
影响因子：
4.7
作者：
Gonnerman, Matthew C.;Benedict, Matthew N.;Price, Nathan D.
通讯作者：
Price, Nathan D.