Molecular characterization of lantibiotic-synthesizing enzyme EpiD reveals a function for bacterial Dfp proteins in coenzyme A biosynthesis.
The lantibiotic-synthesizing flavoprotein EpiD catalyzes the oxidative decarboxylation of peptidylcysteines to peptidyl-aminoenethiols. The sequence motif responsible for flavin coenzyme binding and enzyme activity is conserved in different proteins from all kingdoms of life. Dfp proteins of eubacteria and archaebacteria and salt tolerance proteins of yeasts and plants belong to this new family of flavoproteins. The enzymatic function of all these proteins was not known, but our experiments suggested that they catalyze a similar reaction like EpiD and/or may have similar substrates and are homododecameric flavoproteins. We demonstrate that the N-terminal domain of the Escherichia coli Dfp protein catalyzes the decarboxylation of (R)-4'-phospho-N-pantothenoylcysteine to 4'-phosphopantetheine. This reaction is essential for coenzyme A biosynthesis.
Kupke
T
T
Lehrstuhl für Mikrobielle Genetik, Universität Tübingen, Auf der Morgenstelle 15, Verfügungsgebäude, 72076 Tübingen, Germany. Thomas.Kupke@t-online.de
Uebele
M
M
Schmid
D
D
Jung
G
G
Blaesse
M
M
Steinbacher
S
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002262:Carboxy-Lyases / Q000378:metabolism; D002850:Chromatography, Gel; D003065:Coenzyme A / Q000096:biosynthesis*; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D005486:Flavin Mononucleotide / Q000378:metabolism; D005420:Flavoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010204:Pantetheine / Q000031:analogs & derivatives / Q000378:metabolism; D010205:Pantothenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D010455:Peptides; D011485:Protein Binding; D011487:Protein Conformation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005420:Flavoproteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D010205:Pantothenic Acid; D010204:Pantetheine; C011967:pantothenylcysteine 4'-phosphate; D005486:Flavin Mononucleotide; D010088:Oxidoreductases; C075971:epidermin decarboxylase; D002262:Carboxy-Lyases; D003545:Cysteine; C003129:4'-phosphopantetheine; D003065:Coenzyme A