Synthetic metabolism approaches: A valuable resource for systems biology

Synthetic biology modifies biological systems with the aim of creating new biological parts, devices, and even organisms. Systems biology deciphers the design principles of biological systems trying to derive the mathematical logic behind biological processes. Although different in their respective research approaches and questions, both disciplines are clearly interconnected. Without sufficient understanding of the biological system, synthetic biology studies cannot be properly designed and conducted. On the other hand, systems biology can profit from new biological systems generated by synthetic biology approaches, which can reveal important insights into cellular processes and allow a better understanding of the principles of life. In this article, we present state-of-the-art synthetic biology approaches that focus on the engineering of synthetic metabolism in microbial hosts and show how their implementation has led to new fundamental discoveries on enzyme reversibility, promiscuity, and "underground metabolism". We further discuss how the combination of rational engineering and adaptive laboratory evolution has enabled the generation of microbes with a synthetic central metabolism, leading to completely new metabolic phenotypes. These organisms provide a great resource for future studies to deepen our systems-level understanding on the principles that govern metabolic networks and evolution.