Overlapping riboflavin supply pathways in bacteria

Abstract

Riboflavin derivatives are essential cofactors for a myriad of flavoproteins. In bacteria, flavins importance extends beyond their role as intracellular protein cofactors, as secreted flavins are a key metabolite in a variety of physiological processes. Bacteria obtain riboflavin through the endogenous riboflavin biosynthetic pathway (RBP) or by the use of importer proteins. Bacteria frequently encode multiple paralogs of the RBP enzymes and as for other micronutrient supply pathways, biosynthesis and uptake functions largely coexist. It is proposed that bacteria shut down biosynthesis and would rather uptake riboflavin when the vitamin is environmentally available. Recently, the overlap of riboflavin provisioning elements has gained attention and the functions of duplicated paralogs of RBP enzymes started to be addressed. Results point towards the existence of a modular structure in the bacterial riboflavin supply pathways. Such structure uses subsets of RBP genes to supply riboflavin for specific functions. Given the importance of riboflavin in intra and extracellular bacterial physiology, this complex array of riboflavin provision pathways may have developed to contend with the various riboflavin requirements. In riboflavin-prototrophic bacteria, riboflavin transporters could represent a module for riboflavin provision for particular, yet unidentified processes, rather than substituting for the RBP as usually assumed.

Identification and characterization of a brilliant yellow pigment produced by Bordetella pertussis

“…Riboflavin is a water‐soluble vitamin and cannot therefore pass through the cell membrane; therefore, B. pertussis should have a membrane transport system for riboflavin. Nine proteins (RibU, RibM, RibN, RibV, RibZ, RfnT, RfuABCD, RibXYZ and ImpX) are known to be riboflavin importers in other bacteria . Of these, RfnT, which is known to be a major riboflavin transporter in several bacterial species, can facilitate the trans‐membrane transport of various substrates, including ions, sugar phosphates, drugs, nucleotides, amino acids and peptides ; B. pertussis Tohama I contains the RfnT homolog BP2600 (47% sequence identity with 92% coverage).…”

“…Nine proteins (RibU, RibM, RibN, RibV, RibZ, RfnT, RfuABCD, RibXYZ and ImpX) are known to be riboflavin importers in other bacteria . Of these, RfnT, which is known to be a major riboflavin transporter in several bacterial species, can facilitate the trans‐membrane transport of various substrates, including ions, sugar phosphates, drugs, nucleotides, amino acids and peptides ; B. pertussis Tohama I contains the RfnT homolog BP2600 (47% sequence identity with 92% coverage). However, only two proteins, namely Bfe in Shewanella oneidensis and YeeO in Escherichia coli, which are members of the Multidrug and Toxic compound Extrusion family, have been reported to be riboflavin exporters .…”

“…Riboflavin is a water-soluble vitamin and cannot therefore pass through the cell membrane; therefore, B. pertussis should have a membrane transport system for riboflavin. Nine proteins (RibU, RibM, RibN, RibV, RibZ, RfnT, RfuABCD, RibXYZ and ImpX) are known to be riboflavin importers in other bacteria (31).…”

The Activation of Mucosal-Associated Invariant T (MAIT) Cells Is Affected by Microbial Diversity and Riboflavin Utilization in vitro

“…60% of all Firmicutes and Actinobacteria in the study of Rodionov et al (2019) were unable to synthesize riboflavin and should therefore be unable to activate MAIT cells, which is in line with our data. Nevertheless, riboflavin is essential for all organisms to synthesize flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) and thus has to be taken up (Gutiérrez-Preciado et al, 2015;García-Angulo, 2017). Accordingly, the reduced riboflavin concentration in the culture supernatant of the non-MAIT cell activating bacterial strains A. caccae, B. longum, B. producta, C. butyricum, and C. ramosum suggests riboflavin uptake and thereby riboflavin auxotrophy.…”

“…Shifting from growth to survival-related metabolism sustains survival under acute stress, whereas changes in community composition are thought to occur as a response to long-term stress (Schimel et al, 2007). In E. coli flavoenzymes are involved in a variety of processes, e.g., oxidative stress response, which is directly associated with acid stress and presumably survival-related metabolism (Maurer et al, 2005;García-Angulo, 2017). FMN and FAD are used for the synthesis of flavoenzymes, which make up to 2% of coded genes (Gutiérrez-Preciado et al, 2015).…”