ARB Group, Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, Magdeburg 39106, Germany.
Nat Commun. 2017 Jun 22;8:15956. doi: 10.1038/ncomms15956.
Computational modelling of metabolic networks has become an established procedure in the metabolic engineering of production strains. One key principle that is frequently used to guide the rational design of microbial cell factories is the stoichiometric coupling of growth and product synthesis, which makes production of the desired compound obligatory for growth. Here we show that the coupling of growth and production is feasible under appropriate conditions for almost all metabolites in genome-scale metabolic models of five major production organisms. These organisms comprise eukaryotes and prokaryotes as well as heterotrophic and photoautotrophic organisms, which shows that growth coupling as a strain design principle has a wide applicability. The feasibility of coupling is proven by calculating appropriate reaction knockouts, which enforce the coupling behaviour. The study presented here is the most comprehensive computational investigation of growth-coupled production so far and its results are of fundamental importance for rational metabolic engineering.
代谢网络的计算建模已经成为生产菌株代谢工程中的一种既定方法。一个经常被用来指导微生物细胞工厂合理设计的关键原则是生长和产物合成的化学计量耦联，这使得所需化合物的生产对于生长是必需的。在这里，我们表明，在五大主要生产生物的基因组尺度代谢模型中，几乎所有代谢物在适当的条件下，生长和产物合成的耦联都是可行的。这些生物包括真核生物和原核生物，以及异养生物和光合自养生物，这表明生长耦联作为一种菌株设计原则具有广泛的适用性。通过计算适当的反应敲除来证明耦联的可行性，这些敲除强制了耦联行为。本文的研究是迄今为止对生长耦联产物的最全面的计算研究，其结果对于理性的代谢工程具有重要的基础意义。
