Abstract
Redox reactions are ubiquitous in biological processes. Enzymes involved in redox metabolism often use cofactors in order to facilitate electron-transfer reactions. Common redox cofactors include micronutrients such as vitamins and metals. By far, while iron is the main metal cofactor, riboflavin is the most important organic cofactor. Notably, the metabolism of iron and riboflavin seem to be intrinsically related across life kingdoms. In bacteria, iron availability influences expression of riboflavin biosynthetic genes. There is documented evidence for riboflavin involvement in surpassing iron-restrictive conditions in some species. This is probably achieved through increase in iron bioavailability by reduction of extracellular iron, improvement of iron uptake pathways and boosting hemolytic activity. In some cases, riboflavin may also work as replacement of iron as enzyme cofactor. In addition, riboflavin is involved in dissimilatory iron reduction during extracellular respiration by some species. The main direct metabolic relationships between riboflavin and iron in bacterial physiology are reviewed here.
Highlights
Redox reactions involving electron transfers among molecules are highly required in central biological processes, from CO2 fixation and oxidative phosphorylation to protein folding and cell signaling
This review focuses on current research on the main metabolic interrelationships between iron and riboflavin in bacteria
By increasing riboflavin production, bacteria may increase the activity of some components of iron acquisition pathways (Figure 1A)
Summary
Redox reactions involving electron transfers among molecules are highly required in central biological processes, from CO2 fixation and oxidative phosphorylation to protein folding and cell signaling. Organisms across kingdoms have conserved a dependence on riboflavin and iron to perform basic processes, mainly based on their redox properties It has been documented a metabolic crosstalk between riboflavin and iron in a number of organisms including animals, plants, yeast, and bacteria (Welkie and Miller, 1960; Buzina et al, 1979; Charoenlarp et al, 1980; Powers et al, 1988; Crossley et al, 2007; Chazarreta-Cifre et al, 2011; Hsu et al, 2011; Zhang Y. et al, 2015; Chen et al, 2017; Xin et al, 2017). In V. cholerae, a phylogenetically related pathogen, the riboflavin regulon presents a high degree of overlap with the iron regulon (Mey et al, 2005; SepúlvedaCisternas et al, 2018) In this bacterium, iron regulates the expression of the RBP genes and of the ribN riboflavin importer in a riboflavin-dependent way. Iron levels may regulate the status of riboflavin provision in a gene-specific fashion and reciprocally, riboflavin exerts regulatory effects over iron acquisition genes
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