Recent advances in elementary flux modes and yield space analysis as useful tools in metabolic network studies

A review of the use of elementary flux modes (EFMs) and their applications in metabolic engineering covered with yield space analysis (YSA) is presented. EFMs are an invaluable tool in mathematical modeling of biochemical processes. They are described from their inception in 1994, followed by various improvements of their computation in later years. YSA constitutes another precious tool for metabolic network modeling, and is presented in details along with EFMs in this article. The application of these techniques is discussed for several case studies of metabolic network modeling provided in respective original articles. The article is concluded by some case studies in which the application of EFMs and YSA turned out to be most useful, such as the analysis of intracellular polyhydroxyalkanoate (PHA) formation and consumption in Cupriavidus necator, including the constraint-based description of the steady-state flux cone of the strain's metabolic network, the profound analysis of a continuous five-stage bioreactor cascade for PHA production by C. necator using EFMs and, finally, the study of metabolic fluxes in the metabolic network of C. necator cultivated on glycerol.