FTMD_NEOFI
ID FTMD_NEOFI Reviewed; 411 AA.
AC A1DA61;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=6-hydroxytryprostatin B O-methyltransferase {ECO:0000303|PubMed:23109474};
DE EC=2.1.1.293 {ECO:0000250|UniProtKB:Q4WAW6};
DE AltName: Full=Fumitremorgin biosynthesis protein D {ECO:0000250|UniProtKB:Q4WAW6};
GN Name=ftmMT {ECO:0000303|PubMed:23109474};
GN Synonyms=ftmD {ECO:0000250|UniProtKB:Q4WAW6}; ORFNames=NFIA_093710;
OS Neosartorya fischeri (strain ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164
OS / JCM 1740 / NRRL 181 / WB 181) (Aspergillus fischerianus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=331117;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1020 / DSM 3700 / CBS 544.65 / FGSC A1164 / JCM 1740 / NRRL 181
RC / WB 181;
RX PubMed=18404212; DOI=10.1371/journal.pgen.1000046;
RA Fedorova N.D., Khaldi N., Joardar V.S., Maiti R., Amedeo P., Anderson M.J.,
RA Crabtree J., Silva J.C., Badger J.H., Albarraq A., Angiuoli S., Bussey H.,
RA Bowyer P., Cotty P.J., Dyer P.S., Egan A., Galens K., Fraser-Liggett C.M.,
RA Haas B.J., Inman J.M., Kent R., Lemieux S., Malavazi I., Orvis J.,
RA Roemer T., Ronning C.M., Sundaram J.P., Sutton G., Turner G., Venter J.C.,
RA White O.R., Whitty B.R., Youngman P., Wolfe K.H., Goldman G.H.,
RA Wortman J.R., Jiang B., Denning D.W., Nierman W.C.;
RT "Genomic islands in the pathogenic filamentous fungus Aspergillus
RT fumigatus.";
RL PLoS Genet. 4:E1000046-E1000046(2008).
RN [2]
RP FUNCTION.
RX PubMed=23109474; DOI=10.1002/cbic.201200523;
RA Mundt K., Wollinsky B., Ruan H.L., Zhu T., Li S.M.;
RT "Identification of the verruculogen prenyltransferase FtmPT3 by a
RT combination of chemical, bioinformatic and biochemical approaches.";
RL ChemBioChem 13:2583-2592(2012).
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:23109474). 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 ftmPS/ftmA (By similarity). Brevianamide F is then
CC prenylated by the prenyltransferase ftmPT1/ftmB in the presence of
CC dimethylallyl diphosphate, resulting in the formation of tryprostatin B
CC (By similarity). The three cytochrome P450 monooxygenases, ftmP450-
CC 1/ftmC, ftmP450-2/ftmE and ftmP450-3/FtmG, are responsible for the
CC conversion of tryprostatin B to 6-hydroxytryprostatin B, tryprostatin A
CC to fumitremorgin C and fumitremorgin C to 12,13-dihydroxyfumitremorgin
CC C, respectively (By similarity). The putative methyltransferase
CC ftmMT/ftmD is expected for the conversion of 6-hydroxytryprostatin B to
CC tryprostatin A (By similarity). FtmPT2/FtmH catalyzes the prenylation
CC of 12,13-dihydroxyfumitre-morgin C in the presence of dimethylallyl
CC diphosphate, resulting in the formation of fumitremorgin B (By
CC similarity). Fumitremorgin B is further converted to verruculogen by
CC ftmOx1/ftmF via the insertion of an endoperoxide bond between the two
CC prenyl moieties (By similarity). Finally, verruculogen is further
CC converted to fumitremorgin A by the verruculogen prenyltransferase
CC ftmPT3 (PubMed:23109474). {ECO:0000250|UniProtKB:Q4WAW6,
CC ECO:0000269|PubMed:23109474}.
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:0000250|UniProtKB:Q4WAW6};
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000250|UniProtKB:Q4WAW6}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q4WAW6}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01020}.
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DR EMBL; DS027694; EAW19751.1; -; Genomic_DNA.
DR RefSeq; XP_001261648.1; XM_001261647.1.
DR AlphaFoldDB; A1DA61; -.
DR SMR; A1DA61; -.
DR STRING; 36630.CADNFIAP00009179; -.
DR PRIDE; A1DA61; -.
DR EnsemblFungi; EAW19751; EAW19751; NFIA_093710.
DR GeneID; 4588681; -.
DR KEGG; nfi:NFIA_093710; -.
DR VEuPathDB; FungiDB:NFIA_093710; -.
DR eggNOG; KOG3178; Eukaryota.
DR HOGENOM; CLU_005533_1_4_1; -.
DR OMA; LSFEHCA; -.
DR OrthoDB; 817726at2759; -.
DR Proteomes; UP000006702; Unassembled WGS sequence.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
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 SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 3: Inferred from homology;
KW Alkaloid metabolism; Methyltransferase; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Virulence.
FT CHAIN 1..411
FT /note="6-hydroxytryprostatin B O-methyltransferase"
FT /id="PRO_0000424130"
FT ACT_SITE 313
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 270
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
SQ SEQUENCE 411 AA; 45863 MW; DD5A7F307367F493 CRC64;
MFNLPEVATR LSQNVELLVD EIDKTGSQPN CGNPTLLGPK GLAARDEIIL AAEKLLQQGR
GPGPSLLSLL ESAVDIGTIQ TLIRLEVPDQ VPPTGSIPYD ALVKKLKTPV APELLQRLIR
FTRLAGFLDE DEEGAVKHSP MSAIFVSDPD SAGQARFMAD FGIRPCSFIY ESIKLDPSGE
ATRQGPLALM AREPGAREGP TFFEVLEKDP VNRNRWHDGM AVHNDSMVRH VADAYDWDTV
KSLVDIGGSE GHVAAVIANA FAHIQITVQD RPEIIEKARQ RVDRHRNITF EEHDFFTPQP
RIADAYFLRL ILHDWNDADC TRIVRQISSA LRPGARLLIM DAVLPEPGEG SLQSERQLRR
SDIGMYTLFS AKERSLVQMR RLVEDCDDRL RFEKLYTPPG SHASMLSWIC E
