Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA.
PLoS Comput Biol. 2012;8(11):e1002762. doi: 10.1371/journal.pcbi.1002762. Epub 2012 Nov 1.
The ability of microbial species to consume compounds found in the environment to generate commercially-valuable products has long been exploited by humanity. The untapped, staggering diversity of microbial organisms offers a wealth of potential resources for tackling medical, environmental, and energy challenges. Understanding microbial metabolism will be crucial to many of these potential applications. Thermodynamically-feasible metabolic reconstructions can be used, under some conditions, to predict the growth rate of certain microbes using constraint-based methods. While these reconstructions are powerful, they are still cumbersome to build and, because of the complexity of metabolic networks, it is hard for researchers to gain from these reconstructions an understanding of why a certain nutrient yields a given growth rate for a given microbe. Here, we present a simple model of biomass production that accurately reproduces the predictions of thermodynamically-feasible metabolic reconstructions. Our model makes use of only: i) a nutrient's structure and function, ii) the presence of a small number of enzymes in the organism, and iii) the carbon flow in pathways that catabolize nutrients. When applied to test organisms, our model allows us to predict whether a nutrient can be a carbon source with an accuracy of about 90% with respect to in silico experiments. In addition, our model provides excellent predictions of whether a medium will produce more or less growth than another (p<10(-6)) and good predictions of the actual value of the in silico biomass production.
微生物物种利用环境中发现的化合物产生具有商业价值的产品的能力长期以来一直被人类利用。微生物生物多样性的未被开发的、惊人的多样性为解决医学、环境和能源挑战提供了丰富的潜在资源。了解微生物代谢将是许多潜在应用的关键。在某些条件下,热力学可行的代谢重建可以使用基于约束的方法来预测某些微生物的生长速率。虽然这些重建非常强大,但它们仍然很难构建,而且由于代谢网络的复杂性,研究人员很难从这些重建中了解为什么某种营养物质会为给定的微生物产生给定的生长速率。在这里,我们提出了一个简单的生物量生产模型,该模型可以准确地再现热力学可行的代谢重建的预测。我们的模型仅使用以下信息:i)营养物质的结构和功能,ii)生物体中存在少量酶,以及 iii)代谢途径中碳流的消耗。当应用于测试生物体时,我们的模型允许我们以约 90%的准确度预测一种营养物质是否可以作为碳源,这是相对于计算机实验而言的。此外,我们的模型还可以很好地预测培养基是否会产生更多或更少的生长(p<10(-6)),并且可以很好地预测计算机生物量生产的实际值。