Department of Biomedical Engineering, Duke University, Durham, NC 27708.
Department of Biology, University of Maryland, College Park, MD 20742.
Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2526-2531. doi: 10.1073/pnas.1716888115. Epub 2018 Feb 20.
Metabolic pathways are often engineered in single microbial populations. However, the introduction of heterologous circuits into the host can create a substantial metabolic burden that limits the overall productivity of the system. This limitation could be overcome by metabolic division of labor (DOL), whereby distinct populations perform different steps in a metabolic pathway, reducing the burden each population will experience. While conceptually appealing, the conditions when DOL is advantageous have not been rigorously established. Here, we have analyzed 24 common architectures of metabolic pathways in which DOL can be implemented. Our analysis reveals general criteria defining the conditions that favor DOL, accounting for the burden or benefit of the pathway activity on the host populations as well as the transport and turnover of enzymes and intermediate metabolites. These criteria can help guide engineering of metabolic pathways and have implications for understanding evolution of natural microbial communities.
代谢途径通常在单个微生物群体中进行工程改造。然而,将异源电路引入宿主会造成巨大的代谢负担,从而限制系统的整体生产力。通过代谢分工(DOL)可以克服这种限制,其中不同的群体执行代谢途径中的不同步骤,从而降低每个群体所经历的负担。虽然从概念上讲很有吸引力,但 DOL 有利的条件尚未得到严格确立。在这里,我们分析了 24 种常见的代谢途径架构,其中可以实施 DOL。我们的分析揭示了定义有利于 DOL 的条件的一般标准,这些标准考虑了宿主群体中途径活性的负担或益处,以及酶和中间代谢物的运输和周转率。这些标准可以帮助指导代谢途径的工程设计,并对理解自然微生物群落的进化具有启示意义。