Mycofactocin biosynthesis: modification of the peptide MftA by the radical S-adenosylmethionine protein MftC.
Mycofactocin is a putative, peptide derived, cofactor that is associated primarily with the Mycobacterium genera including the pathogen M. tuberculosis. The pathway consists of the three genes mftA, mftB, and mftC that encode for the peptide substrate, peptide chaperone, and a radical S-adenosylmethionine protein (RS), respectively. Here, we show that the MftB acts as a peptide chaperone, binding MftA with a submicromolar KD (~ 100 nm) and MftC with a low micromolar KD (~ 2 μm). Moreover, we demonstrate that MftC is a radical S-adenosylmethionine (SAM) enzyme. Finally, we show that MftC catalyzes the oxidative decarboxylation of the peptide MftA.
Department of Chemistry and Biochemistry, University of Denver, CO, USA.
Bulat
B
Khaliullin
Department of Chemistry and Biochemistry, University of Denver, CO, USA.
Priyanka
P
Aggarwal
Department of Chemistry and Biochemistry, University of Denver, CO, USA.
Michael
M
Bubas
Department of Chemistry and Biochemistry, University of Denver, CO, USA.
Gareth R
GR
Eaton
Department of Chemistry and Biochemistry, University of Denver, CO, USA.
Sandra S
SS
Eaton
Department of Chemistry and Biochemistry, University of Denver, CO, USA.
John A
JA
Latham
D002384:Catalysis; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000235:genetics*; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity; D019911:Mycobacterium ulcerans / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D011485:Protein Binding; D011497:Protein O-Methyltransferase / Q000737:chemistry / Q000235:genetics*; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D007506:Iron-Sulfur Proteins; D018832:Molecular Chaperones; D010455:Peptides; D012436:S-Adenosylmethionine; D011497:Protein O-Methyltransferase
mycofactocin; peptide interaction; radical S-adenosylmethionine