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Significance The metabolic diversity across the tree of life has become increasingly apparent with the growing availability of sequenced genomes and annotations. The basis for such metabolic diversity in organisms is not understood. Here, we evaluate alternative pathways in amino acid biosynthesis from a standpoint of tradeoff between thermodynamic favorability and cofactor-use efficiency. Using 5,203 sequenced genomes and available metabolic network reconstructions, we found evidence that this tradeoff affects pathway choice, which can be related to organism lifestyle. Given the fundamental importance of metabolism on organism survival and adaptation, such choices help us reveal the impact of selection pressures and may ultimately have fundamental implications for our understanding of the phylogenetic tree.

Thermodynamic favorability and pathway yield as evolutionary tradeoffs in biosynthetic pathway choice