FTMD_ASPFU
ID FTMD_ASPFU Reviewed; 342 AA.
AC Q4WAW6;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=6-hydroxytryprostatin B O-methyltransferase {ECO:0000303|PubMed:23649274};
DE EC=2.1.1.293 {ECO:0000269|PubMed:23649274};
DE AltName: Full=Fumitremorgin biosynthesis protein D {ECO:0000303|PubMed:23649274};
GN Name=ftmMT {ECO:0000303|PubMed:23649274};
GN Synonyms=ftmD {ECO:0000303|PubMed:23649274}; ORFNames=AFUA_8G00200;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION.
RX PubMed=16000710; DOI=10.1099/mic.0.27962-0;
RA Grundmann A., Li S.M.;
RT "Overproduction, purification and characterization of FtmPT1, a
RT brevianamide F prenyltransferase from Aspergillus fumigatus.";
RL Microbiology 151:2199-2207(2005).
RN [3]
RP FUNCTION.
RX PubMed=16755625; DOI=10.1002/cbic.200600003;
RA Maiya S., Grundmann A., Li S.M., Turner G.;
RT "The fumitremorgin gene cluster of Aspergillus fumigatus: identification of
RT a gene encoding brevianamide F synthetase.";
RL ChemBioChem 7:1062-1069(2006).
RN [4]
RP FUNCTION.
RX PubMed=18683158; DOI=10.1002/cbic.200800240;
RA Grundmann A., Kuznetsova T., Afiyatullov S.S., Li S.M.;
RT "FtmPT2, an N-prenyltransferase from Aspergillus fumigatus, catalyses the
RT last step in the biosynthesis of fumitremorgin B.";
RL ChemBioChem 9:2059-2063(2008).
RN [5]
RP FUNCTION.
RX PubMed=19226505; DOI=10.1002/cbic.200800787;
RA Kato N., Suzuki H., Takagi H., Asami Y., Kakeya H., Uramoto M., Usui T.,
RA Takahashi S., Sugimoto Y., Osada H.;
RT "Identification of cytochrome P450s required for fumitremorgin biosynthesis
RT in Aspergillus fumigatus.";
RL ChemBioChem 10:920-928(2009).
RN [6]
RP FUNCTION.
RX PubMed=19763315; DOI=10.1039/b908392h;
RA Steffan N., Grundmann A., Afiyatullov S., Ruan H., Li S.M.;
RT "FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase,
RT catalyses the endoperoxide formation of verruculogen in Aspergillus
RT fumigatus.";
RL Org. Biomol. Chem. 7:4082-4087(2009).
RN [7]
RP FUNCTION.
RX PubMed=21105662; DOI=10.1021/ja106817c;
RA Jost M., Zocher G., Tarcz S., Matuschek M., Xie X., Li S.M., Stehle T.;
RT "Structure-function analysis of an enzymatic prenyl transfer reaction
RT identifies a reaction chamber with modifiable specificity.";
RL J. Am. Chem. Soc. 132:17849-17858(2010).
RN [8]
RP FUNCTION.
RX PubMed=23090579; DOI=10.1039/c2ob26149a;
RA Wollinsky B., Ludwig L., Xie X., Li S.M.;
RT "Breaking the regioselectivity of indole prenyltransferases: identification
RT of regular C3-prenylated hexahydropyrrolo[2,3-b]indoles as side products of
RT the regular C2-prenyltransferase FtmPT1.";
RL Org. Biomol. Chem. 10:9262-9270(2012).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND
RP PATHWAY.
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=23649274; DOI=10.1271/bbb.130026;
RA Kato N., Suzuki H., Okumura H., Takahashi S., Osada H.;
RT "A point mutation in ftmD blocks the fumitremorgin biosynthetic pathway in
RT Aspergillus fumigatus strain Af293.";
RL Biosci. Biotechnol. Biochem. 77:1061-1067(2013).
CC -!- FUNCTION: 6-hydroxytryprostatin B O-methyltransferase; part of the gene
CC cluster that mediates the biosynthesis of fumitremorgins, indole
CC alkaloids that carry not only intriguing chemical structures, but also
CC interesting biological and pharmacological activities
CC (PubMed:23649274). The biosynthesis of fumitremorgin-type alkaloids
CC begins by condensation of the two amino acids L-tryptophan and L-
CC proline to brevianamide F, catalyzed by the non-ribosomal peptide
CC synthetase ftmA (PubMed:16755625). Brevianamide F is then prenylated by
CC the prenyltransferase ftmPT1/ftmB in the presence of dimethylallyl
CC diphosphate, resulting in the formation of tryprostatin B
CC (PubMed:16000710, PubMed:21105662, PubMed:23090579). The three
CC cytochrome P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and
CC ftmP450-3/FtmG, are responsible for the conversion of tryprostatin B to
CC 6-hydroxytryprostatin B, tryprostatin A to fumitremorgin C and
CC fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively
CC (PubMed:19226505). The putative methyltransferase ftmMT/ftmD is
CC expected for the conversion of 6-hydroxytryprostatin B to tryprostatin
CC A (Probable). FtmPT2/FtmH catalyzes the prenylation of 12,13-
CC dihydroxyfumitre-morgin C in the presence of dimethylallyl diphosphate,
CC resulting in the formation of fumitremorgin B (PubMed:18683158).
CC Fumitremorgin B is further converted to verruculogen by ftmOx1/ftmF via
CC the insertion of an endoperoxide bond between the two prenyl moieties
CC (PubMed:19763315). In some fungal species, verruculogen is further
CC converted to fumitremorgin A, but the enzymes involved in this step
CC have not been identified yet (Probable). {ECO:0000269|PubMed:16000710,
CC ECO:0000269|PubMed:16755625, ECO:0000269|PubMed:18683158,
CC ECO:0000269|PubMed:19226505, ECO:0000269|PubMed:19763315,
CC ECO:0000269|PubMed:21105662, ECO:0000269|PubMed:23090579,
CC ECO:0000269|PubMed:23649274, ECO:0000305, ECO:0000305|PubMed:16000710}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-hydroxytryprostatin B + S-adenosyl-L-methionine = H(+) + S-
CC adenosyl-L-homocysteine + tryprostatin A; Xref=Rhea:RHEA:37903,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:72761, ChEBI:CHEBI:72762; EC=2.1.1.293;
CC Evidence={ECO:0000269|PubMed:23649274};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.5 uM for S-adenosyl-L-methionine {ECO:0000269|PubMed:23649274};
CC KM=120 uM for 6-hydroxytryprostatin B {ECO:0000269|PubMed:23649274};
CC Note=kcat is 8.2 sec(-1) with 6-hydroxytryprostatin B as substrate.
CC kcat is 6.9 sec(-1) with S-adenosyl-L-methionine as substrate.;
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:23649274}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23649274}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01020}.
CC -!- CAUTION: In contrast to other A.fumigatus strains, strain ATCC MYA-4609
CC does not produce indole alkaloids such as fumitremorgins and
CC verruculogen. While the biosynthetic pathway is complete, a variation
CC in this enzyme abolishes production of the tryprostatin A intermediate.
CC The weak methyltransferase activity is probably due to the presence of
CC Leu-202 instead of an Arg residue that affects the binding of 6-
CC hydroxytryprostatin B (PubMed:23649274). {ECO:0000305|PubMed:23649274}.
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DR EMBL; AAHF01000014; EAL85146.1; -; Genomic_DNA.
DR RefSeq; XP_747184.1; XM_742091.1.
DR AlphaFoldDB; Q4WAW6; -.
DR SMR; Q4WAW6; -.
DR STRING; 746128.CADAFUBP00008412; -.
DR EnsemblFungi; EAL85146; EAL85146; AFUA_8G00200.
DR GeneID; 3504531; -.
DR KEGG; afm:AFUA_8G00200; -.
DR VEuPathDB; FungiDB:Afu8g00200; -.
DR eggNOG; KOG3178; Eukaryota.
DR HOGENOM; CLU_005533_1_0_1; -.
DR InParanoid; Q4WAW6; -.
DR OMA; LSFEHCA; -.
DR OrthoDB; 817726at2759; -.
DR BRENDA; 2.1.1.293; 508.
DR Proteomes; UP000002530; Chromosome 8.
DR GO; GO:0008171; F:O-methyltransferase activity; IDA:AspGD.
DR GO; GO:1900772; P:fumitremorgin B biosynthetic process; IMP:AspGD.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:1902181; P:verruculogen biosynthetic process; IDA:GO_Central.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR PIRSF; PIRSF005739; O-mtase; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase; Virulence.
FT CHAIN 1..342
FT /note="6-hydroxytryprostatin B O-methyltransferase"
FT /id="PRO_0000424128"
FT ACT_SITE 244
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 201
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
SQ SEQUENCE 342 AA; 38436 MW; 86BBB3C892654210 CRC64;
MTQAVDIGTI QTLIRLEVPD QVPLTGSIPY DALVKKLKTP VDPELLQRLI RFTRLVGFLD
EDAEGAVKHS PMSAIFVNDP DTAGQARFMA DFGIRPCSFI YESIKLDPSG EAARQGPLAL
MAREPGAREG PTFFEVLEKD PVNRKRWHDG MAVHNDSMVR HVAGAYDWGT VQSLVDIGGS
EGHVAAVIVN AFPHIQITVQ DLPEIIEKAR QRGDRHPNII FEEHDFFTPQ PRIADAYFLR
LILHDWNDAD CTRIVRQISS ALRPGARLLI MDAVLPEPGE GSLQSERRLR RSDIGMYTLF
SAKERSLAQM RRLVEDCDSR LRFEKLYTPP GSHASMLSWI CE
