The Monofunctional FMN Riboswitch-Binding Regulator RibR From Bacillus amyloliquefaciens Promotes Riboflavin Biosynthesis.

Flavin mononucleotide (FMN) riboswitches are RNA-based regulatory elements found in many bacteria. FMN riboswitches control genes responsible for the biosynthesis and transport of riboflavin (rib genes). Riboflavin (vitamin B2) is the precursor of the flavoenzyme cofactors FMN and flavin adenine dinucleotide (FAD), and it is FMN (not riboflavin or FAD) that is perceived by FMN riboswitches as a signal with regard to flavin homeostasis. When FMN levels are adequate, expression of rib genes is shut down by FMN riboswitches. The bifunctional protein RibR from the Gram-positive bacterium Bacillus subtilis contains an enzymatic and a regulatory part and is induced when cells encounter specific sulfur sources. Under these conditions, B. subtilis RibR binds to FMN riboswitches, overrides their genetic decisions, and stimulates rib gene expression. In B. subtilis, the objective of this RibR-mediated superordinate control is to link sulfur metabolism to riboflavin metabolism. B. subtilis RibR was previously the only known riboswitch-modulating protein. We now report on a similar but monofunctional protein from Bacillus amyloliquefaciens. RibR from B. amyloliquefaciens contains a regulatory/RNA-binding part only, and ribR expression is not stimulated by sulfur sources but by the disulfide-generating and oxidative stress-inducing compound diamide. RibR-like regulator proteins may be more widespread than anticipated and apparently have evolved to connect riboswitch-controlled pathways to other pathways.