Glycine is an essential one-carbon (C1) metabolite nested in a complex network of cellular metabolism. Glycine and its related metabolic pathways have important biochemical and biomedical implications and have thus been studied for a long time. However, quantitative and systems level knowledge about the interactions and regulations of the pathways are severely limited, especially for the purpose of reengineering the relevant pathways for C1-based biotechnological processes using synthetic biology and metabolic engineering approaches. In fact, quantitative analytic methods are missing for some of the key players of the glycine-related pathways, prominently the glycine cleavage system and folate cycle, particularly for intracellular processes under physiological conditions. Here, we pinpoint the existing gaps and highlight the need and challenges for future development.
