ID   MFTA_MYCS2              Reviewed;          31 AA.
AC   A0QSB6;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2021, sequence version 2.
DT   25-MAY-2022, entry version 84.
DE   RecName: Full=Mycofactocin precursor peptide {ECO:0000305|PubMed:27158836};
GN   Name=mftA {ECO:0000303|PubMed:27158836};
GN   OrderedLocusNames=MSMEG_1421 {ECO:0000312|EMBL:ABK75244.1};
OS   Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS   smegmatis).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycolicibacterium.
OX   NCBI_TaxID=246196;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700084 / mc(2)155;
RA   Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA   Fraser C.M.;
RL   Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION, AND DECARBOXYLATION.
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=27158836; DOI=10.1021/acs.biochem.6b00355;
RA   Bruender N.A., Bandarian V.;
RT   "The Radical S-Adenosyl-L-methionine Enzyme MftC Catalyzes an Oxidative
RT   Decarboxylation of the C-Terminus of the MftA Peptide.";
RL   Biochemistry 55:2813-2816(2016).
RN   [3]
RP   CLEAVAGE.
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=28077628; DOI=10.1074/jbc.m116.762062;
RA   Bruender N.A., Bandarian V.;
RT   "The Creatininase Homolog MftE from Mycobacterium smegmatis Catalyzes a
RT   Peptide Cleavage Reaction in the Biosynthesis of a Novel Ribosomally
RT   Synthesized Post-translationally Modified Peptide (RiPP).";
RL   J. Biol. Chem. 292:4371-4381(2017).
RN   [4]
RP   CLEAVAGE.
RC   STRAIN=ATCC 700084 / mc(2)155;
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).
RN   [5]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 700084 / mc(2)155;
RX   PubMed=31113891; DOI=10.1128/mbio.00190-19;
RA   Krishnamoorthy G., Kaiser P., Lozza L., Hahnke K., Mollenkopf H.J.,
RA   Kaufmann S.H.E.;
RT   "Mycofactocin Is Associated with Ethanol Metabolism in Mycobacteria.";
RL   MBio 10:E00190-E00190(2019).
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 (PubMed:27158836).
CC       Is required for the in vivo ethanol assimilation in M.smegmatis
CC       (PubMed:31113891). {ECO:0000269|PubMed:27158836,
CC       ECO:0000269|PubMed:31113891}.
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:27158836, ECO:0000269|PubMed:28077628,
CC       ECO:0000269|PubMed:30183269}.
CC   -!- DISRUPTION PHENOTYPE: Cells lacking this gene lose the ability to
CC       utilize ethanol as the sole growth substrate.
CC       {ECO:0000269|PubMed:31113891}.
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=ABK75244.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; CP000480; ABK75244.1; ALT_INIT; Genomic_DNA.
DR   RefSeq; WP_029104568.1; NZ_SIJM01000016.1.
DR   RefSeq; YP_885804.1; NC_008596.1.
DR   AlphaFoldDB; A0QSB6; -.
DR   STRING; 246196.MSMEI_1386; -.
DR   EnsemblBacteria; ABK75244; ABK75244; MSMEG_1421.
DR   GeneID; 66732880; -.
DR   KEGG; msm:MSMEG_1421; -.
DR   PATRIC; fig|246196.19.peg.1408; -.
DR   eggNOG; ENOG5031XER; Bacteria.
DR   Proteomes; UP000000757; Chromosome.
DR   InterPro; IPR023988; MftA.
DR   TIGRFAMs; TIGR03969; mycofactocin; 1.
PE   1: Evidence at protein level;
KW   Reference proteome.
FT   CHAIN           1..31
FT                   /note="Mycofactocin precursor peptide"
FT                   /id="PRO_0000452056"
FT   SITE            29..30
FT                   /note="Cleavage; by MftE"
FT                   /evidence="ECO:0000269|PubMed:28077628,
FT                   ECO:0000269|PubMed:30183269"
SQ   SEQUENCE   31 AA;  3453 MW;  E9CAFA975364D6F7 CRC64;
     MEPNQHVEAE TELVTETLVE EVSIDGMCGV Y