MFTA_MYCUA
ID MFTA_MYCUA Reviewed; 30 AA.
AC P0DUE9;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 1.
DT 25-MAY-2022, entry version 4.
DE RecName: Full=Mycofactocin precursor peptide {ECO:0000303|PubMed:27312813};
GN Name=mftA {ECO:0000303|PubMed:27312813, ECO:0000303|PubMed:28634235};
GN OrderedLocusNames=MUL_0771.1 {ECO:0000305};
OS Mycobacterium ulcerans (strain Agy99).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium.
OX NCBI_TaxID=362242;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Agy99;
RX PubMed=17210928; DOI=10.1101/gr.5942807;
RA Stinear T.P., Seemann T., Pidot S., Frigui W., Reysset G., Garnier T.,
RA Meurice G., Simon D., Bouchier C., Ma L., Tichit M., Porter J.L., Ryan J.,
RA Johnson P.D.R., Davies J.K., Jenkin G.A., Small P.L.C., Jones L.M.,
RA Tekaia F., Laval F., Daffe M., Parkhill J., Cole S.T.;
RT "Reductive evolution and niche adaptation inferred from the genome of
RT Mycobacterium ulcerans, the causative agent of Buruli ulcer.";
RL Genome Res. 17:192-200(2007).
RN [2]
RP FUNCTION, INTERACTION WITH MFTB, AND DECARBOXYLATION.
RC STRAIN=Agy99;
RX PubMed=27312813; DOI=10.1002/1873-3468.12249;
RA Khaliullin B., Aggarwal P., Bubas M., Eaton G.R., Eaton S.S., Latham J.A.;
RT "Mycofactocin biosynthesis: modification of the peptide MftA by the radical
RT S-adenosylmethionine protein MftC.";
RL FEBS Lett. 590:2538-2548(2016).
RN [3]
RP FUNCTION, MUTAGENESIS OF VAL-29 AND TYR-30, DECARBOXYLATION, AND
RP TYRAMINE-VALINE CROSS-LINK.
RC STRAIN=Agy99;
RX PubMed=28634235; DOI=10.1074/jbc.m117.795682;
RA Khaliullin B., Ayikpoe R., Tuttle M., Latham J.A.;
RT "Mechanistic elucidation of the mycofactocin-biosynthetic radical S-
RT adenosylmethionine protein, MftC.";
RL J. Biol. Chem. 292:13022-13033(2017).
RN [4]
RP CLEAVAGE.
RC STRAIN=Agy99;
RX PubMed=30183269; DOI=10.1021/acs.biochem.8b00816;
RA Ayikpoe R., Salazar J., Majestic B., Latham J.A.;
RT "Mycofactocin Biosynthesis Proceeds through 3-Amino-5-[(p-
RT hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone (AHDP); Direct
RT Observation of MftE Specificity toward MftA.";
RL Biochemistry 57:5379-5383(2018).
CC -!- FUNCTION: Precursor peptide that leads to mycofactocin (MFT) after
CC extensive post-translational modifications by enzymes encoded by
CC adjacent genes. Mycofactocin acts as a redox cofactor of nicotinamide-
CC dependent oxidoreductases encoded in the same locus.
CC {ECO:0000269|PubMed:27312813, ECO:0000269|PubMed:28634235}.
CC -!- SUBUNIT: Interacts with MftB. {ECO:0000269|PubMed:27312813}.
CC -!- PTM: The post-translational modifications that lead to mycofactocin
CC involve oxidative decarboxylation of the C-terminal tyrosine residue
CC catalyzed by MftC, introduction of a tyramine-valine cross-link,
CC removal of the modified C-terminal dipeptide by MftE. The released
CC dipeptide then undergoes oxidative deamination by MftD, glycosylation
CC by MftF and methylation by an unknown enzyme.
CC {ECO:0000269|PubMed:27312813, ECO:0000269|PubMed:28634235,
CC ECO:0000269|PubMed:30183269}.
CC -!- MISCELLANEOUS: Mycofactocin is classified as a ribosomally synthesized
CC and post-translationally modified peptide (RiPP). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the mycofactocin precursor peptide family.
CC {ECO:0000305}.
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DR EMBL; CP000325; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; WP_071498352.1; NC_008611.1.
DR AlphaFoldDB; P0DUE9; -.
DR Proteomes; UP000000765; Chromosome.
DR InterPro; IPR023988; MftA.
DR TIGRFAMs; TIGR03969; mycofactocin; 1.
PE 1: Evidence at protein level;
FT CHAIN 1..30
FT /note="Mycofactocin precursor peptide"
FT /id="PRO_0000452057"
FT SITE 28..29
FT /note="Cleavage; by MftE"
FT /evidence="ECO:0000269|PubMed:30183269"
FT MUTAGEN 29
FT /note="V->A: Accumulation of decarboxylated tyrosine
FT intermediate."
FT /evidence="ECO:0000269|PubMed:28634235"
FT MUTAGEN 30
FT /note="Y->F: Loss of MftA decarboxylation by MftC."
FT /evidence="ECO:0000269|PubMed:28634235"
SQ SEQUENCE 30 AA; 3307 MW; D6520D17C8EC966A CRC64;
MDRETEAETA ELVTESLVEE VSIDGMCGVY