A lipocalin protein from Bacteroides thetaiotaomicron , a microbiome model species, binds heme and mesoporphyrin IX

How the human microbiome processes heme remains unclear. A prolific model gut organism, Bacteroides thetaiotamicron, was recently reported to dechelate heme b, yielding Fe(II) and protoporphyrin IX. BT0498 is a previously uncharacterized, lipocalin-family protein located directly downstream of the characterized portion of the heme utilization (hmu) operon. We report its expression for the first time, along with UV/visible absorbance titration data showing the protein’s ability to bind both heme and mesoporphyrin IX, the substrate and an analog of the dechelation product, with low-micromolar dissociation constants. AlphaFold 3 modeling of apo- and holo-BT0498 identified potential heme-binding sites and implicated residues involved in coordinating the iron ion. The titrimetric data and AlphaFold models, in conjunction with the encoding gene’s location in the genome, suggest BT0498 may play a role in heme uptake and/or metabolism by Bacteroides thetaiotaomicron and the many related species that share genes encoding both Hmu and BT0498 proteins.