Genome-scale metabolic models applied for human health and biopharmaceutical engineering

Over the last 15 years, genome-scale metabolic models (GEMs) have been reconstructed for human and model animals, such as mouse and rat, to systematically understand metabolism, simulate multicellular or multi-tissue interplay, understand human diseases, and guide cell factory design for biopharmaceutical protein production. Here, we describe how metabolic networks can be represented using stoichiometric matrices and well-defined constraints for flux simulation. Then, we review the history of GEM development for quantitative understanding of Homo sapiens and other relevant animals, together with their applications. We describe how model develops from H. sapiens to other animals and from generic purpose to precise context-specific simulation. The progress of GEMs for animals greatly expand our systematic understanding of metabolism in human and related animals. We discuss the difficulties and present perspectives on the GEM development and the quest to integrate more biological processes and omics data for future research and translation. We truly hope that this review can inspire new models developed for other mammalian organisms and generate new algorithms for integrating big data to conduct more in-depth analysis to further make progress on human health and biopharmaceutical engineering.