• BtuJ1 is a lipoprotein from Bacteroides thetaiotaomicron that binds diverse corrinoids with low nanomolar affinity. • Corrinoid-binding homologues of BtuJ are widespread and frequently duplicated in Bacteroidota. • BtuJ1 enhances fitness under vitamin B 12 limitation and forms an extracellular reservoir for B 12 when the vitamin is scarce. • X-ray crystal structures show binding of BtuJ1 to both B 12 and cyanocobalamin. The acquisition of vitamin B 12 and related cobamides is a key determinant for the fitness of Bacteroidota in the gut. Depending on the species, this uptake process relies on one to four transport systems centered on conserved core outer membrane (OM) complexes composed of the TonB-dependent transporter BtuB and the surface-exposed lipoprotein BtuG. Additionally, the surface-exposed lipoprotein BtuH, although not tightly associated with the BtuBG complex, contributes to cobamide uptake and provides a fitness advantage. Here, we report the functional and structural characterization of BtuJ1 from Bacteroides thetaiotaomicron (B. theta) , an additional surface-exposed lipoprotein in B 12 uptake loci. BtuJ1 binds vitamin B 12 and cobinamide (an intermediate in B 12 biosynthesis) with low nM affinity, conferring a fitness advantage in B 12 -limited environments. Regardless of B 12 availability, BtuJ1 is the most abundant of the B 12 -transport components encoded by B. theta . Under B 12 -replete conditions, BtuJ1 binds the vitamin, generating a readily available pool for transfer to the core BtuBG transport systems during periods of B 12 depletion as demonstrated by in vitro and in vivo B 12 transfer experiments. Together, these findings expand the known functionalities of the diverse accessory OM proteins employed by Bacteroidota and underscore the sophisticated strategies these human gut commensals use to secure vitamin B 12 in the competitive environment of the human gut.
Abellon-Ruiz et al. (Sun,) studied this question.