Amino acid and nucleotide metabolism 1 shape the selection of trophic levels in 2 animals 3

19 What an animal eats determines its trophic level (TL) in the food web. The diet of high-TL animals is 20 thought to contain more energy because it contains higher levels of lipids. This however has not been 21 systematically examined in the context of comprehensive metabolic networks of different animals. 22 Here, we reconstruct species-specific genome-scale metabolic models (GEMs) of 32 animals, and 23 calculate the maximum ATP production per unit of food for each animal. Surprisingly, we find that 24 ATP production is closely associated with metabolic flux through central carbon metabolism and 25 amino acid metabolism, while correlation with lipid metabolism is low. Further, metabolism of 26 specific amino acids and nucleotides underlie maximum ATP production from food. Our analyses 27 indicate that amino acid and nucleotide metabolism, rather than lipid metabolism, are major 28 contributors to the selection of animal trophic levels, demonstrating that species-level metabolic flux 29 plays key roles in trophic interactions and evolution. 30 . CC-BY-NC-ND 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is The copyright holder for this preprint this version posted July 3, 2021. ; https://doi.org/10.1101/2021.07.01.450789 doi: bioRxiv preprint

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