BBB seminar: Matthias Mack

Part 1) FMN riboswitches are not “alone”: The FMN riboswitch of Bacillus subtilis is controlled by the protein RibR
Part 2) FMN riboswitches as targets for the antibiotic roseoflavin synthesized by Streptomyces davawensis

Matthias Mack
Mannheim University of Applied Sciences, Germany

In the first part of my talk I will introduce you to the regulation of riboflavin (vitamin B2) biosynthesis in bacteria and to cis-acting genetic elements which are called “FMN riboswitches” (FMN = flavin mononucleotide; FMN is a cofactor of a variety of flavoproteins/flavoenzymes). Riboswitches were thought to be RNAs that directly monitor a physiological signal without the “help” of any other cellular factor (such as a regulatory protein). We now show (for the first time) that a protein (RibR from Bacillus subtilis) is able to modulate genetic decisions made by FMN riboswitches and also found a reason for this “secondary” metabolic control.

In the second half of my presentation I will report on the mechanism of action of the antibiotic roseoflavin. Roseoflavin is a riboflavin analog which targets FMN riboswitches (and, by the way, also flavoproteins) which links the following “roseoflavin story” to the first part of my talk. Roseoflavin is the only known natural riboflavin analog with antibiotic function and is produced by the bacteria Streptomyces davawensis and Streptomyces cinnabarinus. We found that roseoflavin is taken up by riboflavin transporters and then is converted to the FMN analog roseoflavin mononucleotide (RoFMN). RoFMN negatively affects the function of FMN riboswitches and essentially leads to a cellular “shortage” in riboflavin. A highly specialized FMN riboswitch, which is not affected by RoFMN, confers roseoflavin resistance to the producer S. davawensis.

Chairperson: Ruth Brenk, Department of Biomedicine