Host cell CRISPR genomics and modelling reveal shared metabolic vulnerabilities in the intracellular development of Plasmodium falciparum and related hemoparasites

Hepatocyte specific model

Starting with the thermodynamically curated human genome-scale Recon 3D^30,31, we reconstructed a hepatocyte metabolic model by taking into account the physiology of hepatocytes and the genes expressed in liver cells. Towards this end, we defined the physiology of hepatocytes by integrating in the human Recon3D model publicly available fluxomics data for 92 boundary reactions²⁸ and metabolomics data for 213 metabolites²⁹ from previous hepatocyte model reconstructions. Additionally, we set the growth rate of the hepatocyte to a maximum of 0.014 h⁻¹ corresponding to a doubling time of 49.5 h⁴⁹ and the ATP maintenance rate to at least 1.07 mmol/gDW/h⁵⁰. The Human Protein Atlas (www.proteinatlas.org)²⁷ was used to identify 1853 metabolic genes present in…