| Summary: | Summary: The metabolic capabilities of cells determine their biotechnological potential, fitness in ecosystems, pathogenic threat levels, and function in multicellular organisms. Their comprehensive experimental characterization is generally not feasible, particularly for unculturable organisms. In principle, the full range of metabolic capabilities can be computed from an organism's annotated genome using metabolic network reconstruction. However, current computational methods cannot deal with genome-scale metabolic networks. Part of the problem is that these methods aim to enumerate all metabolic pathways, while computation of all (elementally balanced) conversions between nutrients and products would suffice. Indeed, the elementary conversion modes (ECMs, defined by Urbanczik and Wagner) capture the full metabolic capabilities of a network, but the use of ECMs has not been accessible until now. We explain and extend the theory of ECMs, implement their enumeration in ecmtool, and illustrate their applicability. This work contributes to the elucidation of the full metabolic footprint of any cell. The Bigger Picture: Understanding the metabolic capabilities of cells is of profound importance. Microbial metabolism shapes global cycles of elements and cleans polluted soils. Human and pathogen metabolism affects our health. Recent advances allow for automatic reconstruction of reaction networks for any organism, which is already used in synthetic biology, (food) microbiology, and agriculture to compute optimal yields from resources to products. However, computational tools are limited to optimal states or subnetworks, leaving many capabilities of organisms hidden. Our program, ecmtool, creates a blueprint of any organism's metabolic functionalities, drastically improving insights obtained from genome sequences. Ecmtool may become essential in exploratory research, especially for studying cells that are not culturable in laboratory conditions. Ideally, elementary conversion mode enumeration will someday be a standard step after metabolic network reconstruction, achieving the metabolic characterization of all known organisms.
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