Department of Molecular Sciences, Macquarie University, Sydney, Australia.
Biomolecular Discovery Research Centre, Macquarie University, Sydney, Australia.
Crit Rev Biotechnol. 2020 Nov;40(7):895-912. doi: 10.1080/07388551.2020.1785386. Epub 2020 Jul 13.
Metabolic engineering is crucial in the development of production strains for platform chemicals, pharmaceuticals and biomaterials from renewable resources. The central carbon metabolism (CCM) of heterotrophs plays an essential role in the conversion of biomass to the cellular building blocks required for growth. Yet, engineering the CCM ultimately aims toward a maximization of flux toward products of interest. The most abundant dissimilative carbohydrate pathways amongst prokaryotes (and eukaryotes) are the Embden-Meyerhof-Parnas (EMP) and the Entner-Doudoroff (ED) pathways, which build the basics for heterotrophic metabolic chassis strains. Although the EMP is regarded as the textbook example of a carbohydrate pathway owing to its central role in production strains like , and , it is either modified, complemented or even replaced by alternative carbohydrate pathways in different organisms. The ED pathway also plays key roles in biotechnological relevant bacteria, like and , and its importance was recently discovered in photoautotrophs and marine microorganisms. In contrast to the EMP, the ED pathway and its variations are not evolutionary optimized for high ATP production and it differs in key principles such as protein cost, energetics and thermodynamics, which can be exploited in the construction of unique metabolic designs. Single ED pathway enzymes and complete ED pathway modules have been used to rewire carbon metabolisms in production strains and for the construction of cell-free enzymatic pathways. This review focuses on the differences of the ED and EMP pathways including their variations and discusses the use of alternative pathway strategies for and cell-free metabolic engineering.
代谢工程在开发可再生资源平台化学品、药物和生物材料的生产菌株方面至关重要。异养生物的中心碳代谢（CCM）在将生物质转化为细胞生长所需的构建块方面起着至关重要的作用。然而，CCM 的工程最终旨在最大限度地提高对感兴趣产物的通量。在原核生物（和真核生物）中最丰富的异化碳水化合物途径是 EMP（Embden-Meyerhof-Parnas）和 ED（Entner-Doudoroff）途径，它们为异养代谢底盘菌株构建了基础。尽管 EMP 被认为是碳水化合物途径的典型范例，因为它在生产菌株如 、 等中起着核心作用，但在不同的生物体中，它要么被修饰、补充，甚至被替代碳水化合物途径所取代。ED 途径在生物技术相关的细菌中也起着关键作用，如 、 等，最近在光自养生物和海洋微生物中发现了它的重要性。与 EMP 不同，ED 途径及其变体不是为了高效产生 ATP 而进化优化的，它在蛋白质成本、能量学和热力学等关键原则上存在差异，这些差异可以在独特代谢设计的构建中得到利用。单一的 ED 途径酶和完整的 ED 途径模块已被用于重新布线生产菌株中的碳代谢，并用于构建无细胞酶途径。本文综述了 ED 和 EMP 途径的差异，包括它们的变体，并讨论了替代途径策略在 和无细胞代谢工程中的应用。
