A Novel N,N-8-Amino-8-demethyl-d-riboflavin Dimethyltransferase (RosA) Catalyzing the Two Terminal Steps of Roseoflavin Biosynthesis in Streptomyces davawensis

Jankowitsch, Frank; Kühm, Christian; Kellner, Roland; Kalinowski, Jörn; Pelzer, Stefan; Macheroux, Peter; Mack, Matthias

doi:10.1074/jbc.m111.292300

Cited by 36 publications

(59 citation statements)

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“…The S. davawensis PAC library obtained as described above was screened by PCR for clones containing the gene rosA, which is involved in roseoflavin biosynthesis (24). First, the PAC library clones were screened for the presence of a 500-bp internal fragment using the oligonucleotides 100rosmfw (5=-GGA GGA ATG GGA CGA GGT GAT GG-3=) and 100rosmrv (5=-GGT TGT CGT AGT AGC GGG CGA T-3=).…”

Section: Strains and Plasmids S Davawensis (Jcm 4913)mentioning

confidence: 99%

“…The high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis of roseoflavin and other flavins was carried out as described previously (24).…”

Section: Strains and Plasmids S Davawensis (Jcm 4913)mentioning

confidence: 99%

“…It was postulated that roseoflavin is synthesized from riboflavin through 8-amino-8-demethyl-riboflavin and 8-methylamino-8-demethyl-riboflavin (25,38). Recently, a novel N,N-dimethyltransferase (encoded by rosA) was reported to catalyze the two sequential S-adenosylmethionine-dependent methylation reactions necessary to convert 8-amino-8-demethyl-riboflavin into roseoflavin (24). The remaining genes (enzymes) of the roseoflavin biosynthetic pathway, however, could not be localized.…”

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Genome Sequence of the Bacterium Streptomyces davawensis JCM 4913 and Heterologous Production of the Unique Antibiotic Roseoflavin

et al. 2012

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Section: Strains and Plasmids S Davawensis (Jcm 4913)mentioning

confidence: 99%

“…The high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis of roseoflavin and other flavins was carried out as described previously (24).…”

Section: Strains and Plasmids S Davawensis (Jcm 4913)mentioning

confidence: 99%

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Genome Sequence of the Bacterium Streptomyces davawensis JCM 4913 and Heterologous Production of the Unique Antibiotic Roseoflavin

et al. 2012

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“…Inactivation of rosA generated a recombinant S. davawensis strain that produces AF (see Fig. S1) (15), which can be employed to synthesize this compound.…”

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“…An as yet unknown phosphatase produces AF from AFMN. Finally, the N,N-8-demethyl-8-aminoriboflavin dimethyltransferase RosA (15,16) catalyzes the formation of RoF from AF and S-adenosylmethionine. Inactivation of rosA generated a recombinant S. davawensis strain that produces AF (see Fig.…”

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Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes

et al. 2016

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The riboflavin analogs roseoflavin (RoF) and 8-demethyl-8-aminoriboflavin (AF) are produced by the bacteria Streptomyces davawensis and Streptomyces cinnabarinus. Riboflavin analogs have the potential to be used as broad-spectrum antibiotics, and we therefore studied the metabolism of riboflavin (vitamin B 2 ), RoF, and AF in the human pathogen Listeria monocytogenes, a bacterium which is a riboflavin auxotroph. We show that the L. monocytogenes protein Lmo1945 is responsible for the uptake of riboflavin, RoF, and AF. Following import, these flavins are phosphorylated/adenylylated by the bifunctional flavokinase/flavin adenine dinucleotide (FAD) synthetase Lmo1329 and adenylylated by the unique FAD synthetase Lmo0728, the first monofunctional FAD synthetase to be described in bacteria. R iboflavin (vitamin B 2 ) is not synthesized by mammals but is synthesized by many microorganisms and by all plants (1).The genomes of the human bacterial pathogens Listeria monocytogenes, Streptococcus pyogenes, and Enterococcus faecalis do not contain genes encoding riboflavin biosynthetic enzymes (2), and thus these microorganisms are riboflavin auxotrophs. L. monocytogenes, Streptococcus pyogenes, and Enterococcus faecalis produce energy-coupling factor (ECF) transporters which combine with a riboflavin-specific binding subunit (subunit EcfS or RibU) (3), and ECF-RibU-mediated uptake is the sole source of riboflavin (4).Riboflavin cannot be detected in cell extracts of bacteria (5-7), indicating that it is completely metabolized by flavokinases (RibF) (EC 2.7.1.26) and FAD synthetases (RibC) (EC 2.7.7.2). These enzymes catalyze the formation of FMN (from riboflavin and ATP) and FAD (from FMN and ATP) (see Fig. S1 in the supplemental material) and play an important role in metabolic trapping of riboflavin (8). In bacteria, bifunctional flavokinases/FAD synthetases have been found, whereas in eukarya and archaea, monofunctional enzymes seem to be the rule (9). FMN and FAD are cofactors of flavoproteins/flavoenzymes, which have a wide variety of different biological functions (10). The number of flavindependent proteins varies greatly in different organisms (and among pathogens) and covers a range from approximately 0.1% to 3.5% of the proteome (11). In Escherichia coli, FMN and FAD are present at levels which are about 30 times lower than those of the highly abundant amino acids or nucleotides (12), whereby FAD (170 M) clearly is present at higher levels than FMN (54

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Natural Flavins: Occurrence, Role, and Noncanonical Chemistry

Drenth¹,

Fraaije²

2021

Flavin‐Based Catalysis

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A Novel N,N-8-Amino-8-demethyl-d-riboflavin Dimethyltransferase (RosA) Catalyzing the Two Terminal Steps of Roseoflavin Biosynthesis in Streptomyces davawensis

Cited by 36 publications

References 31 publications

Genome Sequence of the Bacterium Streptomyces davawensis JCM 4913 and Heterologous Production of the Unique Antibiotic Roseoflavin

Genome Sequence of the Bacterium Streptomyces davawensis JCM 4913 and Heterologous Production of the Unique Antibiotic Roseoflavin

Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes

Natural Flavins: Occurrence, Role, and Noncanonical Chemistry

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