2025/05/24 by Anastasia Sveshnikova, Omid Oftadeh, Vassily Hatzimanikatis · 1 voice
Biochemistry, Genetics and Molecular Biology · #Enzyme Catalysis and Immobilization #Microbial Metabolic Engineering and Bioproduction #Plant biochemistry and biosynthesis
paper · pdf · doi:10.1038/s41467-025-59827-7
openalex publication_date 2025/05/24 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/03
The synthesis of many important biochemicals involves complex molecules and numerous reactions. The design and optimization of whole-cell biocatalysts for the production of these molecules requires metabolic modeling to extract production pathways from biochemical databases and integrate them into genome-scale models of the host. However, the synthesis of such complex molecules often requires reactions from multiple pathways operating in balanced subnetworks that are not assembled in existing databases. Here, we present SubNetX, a computational algorithm that extracts reactions from a database and assembles balanced subnetworks to produce a target biochemical from selected precursor metabolites, energy currencies, and cofactors. These subnetworks can be integrated into whole-cell models, allowing the reconstruction and ranking of alternative biosynthetic pathways based on yield, length, and other design goals. We apply SubNetX to 70 industrially relevant natural and synthetic chemicals to demonstrate the application of this pipeline.