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Literature summary extracted from

  • Ayikpoe, R.; Govindarajan, V.; Latham, J.A.
    Occurrence, function, and biosynthesis of mycofactocin (2019), Appl. Microbiol. Biotechnol., 103, 2903-2912 .
    View publication on PubMedView publication on EuropePMC

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
3.4.14.14 Fe2+ iron-dependent peptidase Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.4.14.14 precursor peptide MftA-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + H2O Mycobacterium tuberculosis the enzyme selectively hydrolyzes the amide bond between Val29 and Gly28 of MftA*, liberating the putative carbon skeleton of mycofactocin, 3-amino-5-[(p-hydroxyphenyl) methyl]-4,4-dimethyl-2-pyrrolidinone MftA(1-28) + 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone
-
 ?
3.4.14.14 precursor peptide MftA-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + H2O Mycobacterium tuberculosis H37Rv the enzyme selectively hydrolyzes the amide bond between Val29 and Gly28 of MftA*, liberating the putative carbon skeleton of mycofactocin, 3-amino-5-[(p-hydroxyphenyl) methyl]-4,4-dimethyl-2-pyrrolidinone MftA(1-28) + 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone
-
 ?
4.1.99.26 C-terminal [mycofactocin precursor peptide]-glycyl-L-valyl-4-[2-aminoethenyl]phenol + S-adenosyl-L-methionine + AH2 Mycobacterium sp.
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 C-terminal [mycofactocin precursor peptide]-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + 5'-deoxyadenosine + L-methionine + A
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.4.14.14 Mycobacterium tuberculosis P9WP59
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-
3.4.14.14 Mycobacterium tuberculosis H37Rv P9WP59
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-
4.1.99.26 Mycobacterium sp.
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-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.14.14 precursor peptide MftA-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + H2O the enzyme selectively hydrolyzes the amide bond between Val29 and Gly28 of MftA*, liberating the putative carbon skeleton of mycofactocin, 3-amino-5-[(p-hydroxyphenyl) methyl]-4,4-dimethyl-2-pyrrolidinone Mycobacterium tuberculosis MftA(1-28) + 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone
-
 ?
3.4.14.14 precursor peptide MftA-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + H2O the enzyme selectively hydrolyzes the amide bond between Val29 and Gly28 of MftA*, liberating the putative carbon skeleton of mycofactocin, 3-amino-5-[(p-hydroxyphenyl) methyl]-4,4-dimethyl-2-pyrrolidinone Mycobacterium tuberculosis H37Rv MftA(1-28) + 3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethyl-2-pyrrolidinone
-
 ?
4.1.99.26 C-terminal [mycofactocin precursor peptide]-glycyl-L-valyl-4-[2-aminoethenyl]phenol + S-adenosyl-L-methionine + AH2
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 Mycobacterium sp. C-terminal [mycofactocin precursor peptide]-glycyl-3-amino-5-[(4-hydroxyphenyl)methyl]-4,4-dimethylpyrrolidin-2-one + 5'-deoxyadenosine + L-methionine + A
-
 ?
4.1.99.26 additional information MftC reductively cleaves SAM to form a 5'-deoxyadenosine radical which in turn abstracts a hydrogen from the Cbeta of the C-terminal tyrosine. Following a subsequent abstraction of an electron from the substrate and the loss of the C-terminal carboxylate a new alpha/beta unsaturated bond is formed on the intermediate MftA**. In the next step of MftC catalysis, a second 5'-deoxyadenosine radical abstracts a hydrogen from the Cbeta of the penultimate valine residue. The Cbeta radical on the valine side chain forms a new bond with the sp2 hybridized C2 of the p-(2-aminoethenyl)phenol. As a result, the product from MftC catalysis, MftA*, contains a C-terminal 3-amino-5-[(p-hydroxyphenyl) methyl]-4,4-dimethyl-2-pyrrolidinone moiety Mycobacterium sp. ?
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Synonyms

EC Number Synonyms Comment Organism
3.4.14.14 mftE
-
 Mycobacterium tuberculosis
3.4.14.14 Rv0695
-
 Mycobacterium tuberculosis
4.1.99.26 mftC
-
 Mycobacterium sp.

Cofactor

EC Number Cofactor Comment Organism Structure
4.1.99.26 S-adenosyl-L-methionine
-
 Mycobacterium sp.

General Information

EC Number General Information Comment Organism
4.1.99.26 evolution architecture and distribution of the mycofactocin biosynthetic cluster, mftABCDEF, among the Actinobacteria phylum, overview. MftC belongs to a RS enzyme subfamily that contains an elongated C-terminal domain annotated as a SPASM domain, members are subtilosin A, pyrroloquinoline quinone, anaerobic sulfatase maturating enzyme, and mycofactocin. PqqE and MftC belong to a select group of RS-SPASM proteins that have been shown to form carbon-carbon bonds on their respective precursor peptide. The proteins associated with the RS-SPASM subfamily are known peptide modifiers that have been shown to catalyze intramolecular C-S bonds and C-C bonds and oxidative decarboxylation reactions on the precursor peptide. The mft cluster is evenly distributed in the genomes of both slow and rapid growing mycobacteria including notable species such as Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium bovis, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium smegmatis, Mycobacterium ulcerans, Mycobacterium marinum, and Mycobacterium vanbaalenii. The average sequence identity of all MftC proteins within the Mycobacterium genus to the Mycobacterium tuberculosis strain H37Rv (Mtb) MftC is as high as 89%. Within the Actinobacteria phylum, the average sequence identity of MftC proteins to that of Mtb MftC remains quite high in genera such as Rhodococcus (79%), Nocardia (77%), Gordonia (79%), and Streptomyces (74%). But the sequence identity of MftC outside of the Actinobacteria undergoes a significant drop-off with averages in a range of 42% to 59% Mycobacterium sp.
4.1.99.26 metabolism enzyme MftC is active in the mycofactocin biosynthetic pathway. Association and distribution of the mft genes. Potential molecular and physiological role of mycofactocin, and known biosynthetic steps involving MftA, MftB, MftC, and MftE in relation to pyrroloquinoline quinone biosynthesis, function of the remaining putative biosynthetic enzymes, MftD and MftF. Expression of the mycofactocin biosynthetic pathway is controlled by the regulator MftR, a member of the TetR family of regulators (TFRs). MftR is the mycofactocin regulator. In the first step of mycofactocin biosynthesis, MftC reductively cleaves SAM to form a 5'-deoxyadenosine radical which in turn abstracts a hydrogen from the Cbeta of the C-terminal tyrosine. Following a subsequent abstraction of an electron from the substrate and the loss of the C-terminal carboxylate, a new alpha/beta unsaturated bond is formed on the intermediate MftA**. In the next step of MftC catalysis, a second 5'-deoxyadenosine radical abstracts a hydrogen from the Cbeta of the penultimate valine residue. The Cbeta radical on the valine side chain forms a new bond with the sp2 hybridized C2 of the p-(2-aminoethenyl)phenol. As a result, the product from MftC catalysis, MftA*, contains a C-terminal 3-amino-5-[(p-hydroxyphenyl) methyl]-4,4-dimethyl-2-pyrrolidinone moiety Mycobacterium sp.
4.1.99.26 physiological function the protein MftC is a putative radical S-adenosylmethionine (RS) enzyme with low sequence homology to the pyrroloquinoline quinone (PQQ) biosynthetic enzyme PqqE Mycobacterium sp.