Fig. 1: Enzymatic conversion of heme to bilirubin and structural features of key pathway enzymes.
From: Systemic engineering and global regulation enabling high-level bilirubin biosynthesis
a Overall reaction pathway from heme to bilirubin (BR), catalyzed sequentially by heme oxygenase (HO) and biliverdin reductase (BVR). b Conformational dynamics of HO and its redox partner (RP) during electron transfer: the closed conformation enables electron transfer from NADPH to FMN, while the open conformation facilitates FMN-mediated electron delivery to the heme-bound HO. c Mechanistic steps of HO-catalyzed heme degradation, including O₂ activation and porphyrin ring cleavage, yielding biliverdin (BV), Fe²⁺, and carbon monoxide (CO). d Alternative forms of redox partners across species, including separate FAD- and FMN-containing proteins that mediate electron transfer via Fe–S clusters. e Structural architecture of BVR, highlighting the Rossmann-fold domain and binding pockets for NADPH and biliverdin. f Proposed mechanism for BV reduction by BVR, involving π-stacked BV molecules and NADPH-mediated hydride transfer. Referenced the crystal structure provided by PDB code: 1DVE (HO, https://doi.org/10.2210/pdb1DVE/pdb), 3ES9 (open conformation of CPR, https://doi.org/10.2210/pdb3ES9/pdb), 5URE (close conformation of CPR, https://doi.org/10.2210/pdb5URE/pdb), 6J79 (fusion protein of CPR and HO, https://doi.org/10.2210/pdb6J79/pdb), 5B3V (BVR, https://doi.org/10.2210/pdb5B3V/pdb), 1PDX ([Fe2-S2] cluster-binding protein, https://doi.org/10.2210/pdb1PDX/pdb), 1Q1R (FAD-dependent oxidoreductase, https://doi.org/10.2210/pdb1Q1R/pdb), 1AHN (Ferredoxin / Flavodoxin, https://doi.org/10.2210/pdb1AHN/pdb), 1FDR (Ferredoxin / Flavodoxin reductase, https://doi.org/10.2210/pdb1FDR/pdb).
