Monod方程作为微生物生长的一般速率规律得到了广泛的应用,但它的应用并不总是成功的。通过借鉴动力学和化学计量代谢模型以及代谢控制分析的框架,这里报道的模型模拟了产甲烷微生物的生长动力学,并说明不同的酶和代谢物在不同程度上控制生长速率,并且它们的控制峰值在非常低的位置,中间,或非常高的底物浓度。相比之下,只有一个术语和两个参数,Monod方程仅近似地解释了在非常高和非常低的底物浓度下速率决定酶和代谢物的控制,但忽略了酶和代谢物,其控制在中等浓度下最显著。这些发现支持Monod方程和产甲烷菌生长之间的有限联系,并统一了关于酶在塑造生长动力学中的作用的竞争观点。结果还排除了从产甲烷菌代谢网络中推导Monod方程的机理,并突出了微生物学中的一个基本挑战:单项表达可能不足以准确预测微生物生长。重要性Monod方程已广泛应用于预测微生物生长速率,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Monod方程和产甲烷菌代谢网络之间的有限机制联系。具体来说,该方程通过在非常低和非常高的底物浓度下确定代谢物和酶的速率来提供对对照的近似,但它缺少其余的酶和代谢物,它们的对照在中等浓度时最显著。这些结果支持Monod方程作为生长速率的有用近似,并强调了微生物动力学中的基本挑战:单项速率表达可能不足以准确预测微生物生长。
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.