PSOF_ASPFU
ID PSOF_ASPFU Reviewed; 905 AA.
AC Q4WAZ0;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Dual-functional monooxygenase/methyltransferase psoF {ECO:0000303|PubMed:24939566};
DE EC=1.-.-.- {ECO:0000269|PubMed:24939566};
DE EC=2.1.1.- {ECO:0000269|PubMed:24939566};
DE AltName: Full=Pseurotin biosynthesis protein F {ECO:0000303|PubMed:24082142};
GN Name=psoF {ECO:0000303|PubMed:24082142}; ORFNames=AFUA_8G00440;
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, AND DISRUPTION PHENOTYPE.
RX PubMed=24082142; DOI=10.1073/pnas.1313258110;
RA Wiemann P., Guo C.J., Palmer J.M., Sekonyela R., Wang C.C., Keller N.P.;
RT "Prototype of an intertwined secondary-metabolite supercluster.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:17065-17070(2013).
RN [3]
RP FUNCTION, DOMAIN, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RX PubMed=24939566; DOI=10.1002/anie.201404804;
RA Tsunematsu Y., Fukutomi M., Saruwatari T., Noguchi H., Hotta K., Tang Y.,
RA Watanabe K.;
RT "Elucidation of pseurotin biosynthetic pathway points to trans-acting C-
RT methyltransferase: generation of chemical diversity.";
RL Angew. Chem. Int. Ed. 53:8475-8479(2014).
CC -!- FUNCTION: Dual-functional monooxygenase/methyltransferase; part of the
CC gene cluster that mediates the biosynthesis of pseurotin A, a
CC competitive inhibitor of chitin synthase and an inducer of nerve-cell
CC proliferation (PubMed:24082142, PubMed:24939566). The PKS-NRPS hybrid
CC synthetase psoA is responsible for the biosynthesis of azaspirene, one
CC of the first intermediates having the 1-oxa-7-azaspiro[4,4]-non-2-ene-
CC 4,6-dione core of pseurotin, via condensation of one acetyl-CoA, 4
CC malonyl-CoA, and a L-phenylalanine molecule (PubMed:24082142,
CC PubMed:24939566). The dual-functional monooxygenase/methyltransferase
CC psoF seems to be involved in the addition of the C3 methyl group onto
CC the pseurotin scaffold (PubMed:24939566). Azaspirene is then converted
CC to synerazol through 4 steps including oxidation of C17 by the
CC cytochrome P450 monooxygenase psoD, O-methylation of the hydroxy group
CC of C8 by the methyltransferase psoC, and the trans-to-cis isomerization
CC of the C13 olefin by the glutathione S-transferase psoE
CC (PubMed:24939566). The fourth step of synerazol production is performed
CC by the dual-functional monooxygenase/methyltransferase psoF which seems
CC to catalyze the epoxidation of the intermediate deepoxy-synerazol
CC (PubMed:24939566). Synerazol can be attacked by a water molecule
CC nonenzymatically at two different positions to yield two diol products,
CC pseurotin A and pseurotin D (PubMed:24939566).
CC {ECO:0000269|PubMed:24082142, ECO:0000269|PubMed:24939566}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:24082142, ECO:0000269|PubMed:24939566}.
CC -!- DOMAIN: PsoF is a unique bifunctional enzyme catalyzing two different
CC types of reactions at completely separate steps of the pseurotin
CC biosynthetic pathway and comprised an unusual combination of two
CC domains, one homologous to a methyltransferase (MT) and another to an
CC FAD-containing monooxygenase (FMO) (PubMed:24939566).
CC {ECO:0000269|PubMed:24939566}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of pseurotin but leads
CC to the accumulation of demethyl-deepoxy-synerazol (PubMed:24082142,
CC PubMed:24939566). {ECO:0000269|PubMed:24082142,
CC ECO:0000269|PubMed:24939566}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the FAD-binding
CC monooxygenase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the class I-like SAM-
CC binding methyltransferase superfamily. {ECO:0000305}.
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DR EMBL; AAHF01000014; EAL85122.1; -; Genomic_DNA.
DR RefSeq; XP_747160.1; XM_742067.1.
DR PDB; 6KJG; X-ray; 1.99 A; A/B/C=538-905.
DR PDB; 6KJI; X-ray; 1.99 A; A/B/C=538-905.
DR PDBsum; 6KJG; -.
DR PDBsum; 6KJI; -.
DR AlphaFoldDB; Q4WAZ0; -.
DR SMR; Q4WAZ0; -.
DR STRING; 746128.CADAFUBP00008391; -.
DR EnsemblFungi; EAL85122; EAL85122; AFUA_8G00440.
DR GeneID; 3504496; -.
DR KEGG; afm:AFUA_8G00440; -.
DR VEuPathDB; FungiDB:Afu8g00440; -.
DR eggNOG; KOG1399; Eukaryota.
DR HOGENOM; CLU_014803_0_0_1; -.
DR InParanoid; Q4WAZ0; -.
DR OMA; RTDGEAW; -.
DR OrthoDB; 405736at2759; -.
DR Proteomes; UP000002530; Chromosome 8.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; IDA:AspGD.
DR GO; GO:0004499; F:N,N-dimethylaniline monooxygenase activity; IEA:InterPro.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:1902086; P:fumagillin biosynthetic process; IGC:AspGD.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.50.50.60; -; 3.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR020946; Flavin_mOase-like.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF00743; FMO-like; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR SUPFAM; SSF51905; SSF51905; 2.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW 3D-structure; FAD; Flavoprotein; Methyltransferase; Monooxygenase; NADP;
KW Oxidoreductase; Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..905
FT /note="Dual-functional monooxygenase/methyltransferase
FT psoF"
FT /id="PRO_0000438200"
FT REGION 12..215
FT /note="FAD-containing monooxygenase (FMO) domain"
FT /evidence="ECO:0000269|PubMed:24939566"
FT REGION 695..876
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000269|PubMed:24939566"
FT BINDING 18
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 45..48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 55..57
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 57
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 63
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 110
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 185..191
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 208..209
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 328..329
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT BINDING 495
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT SITE 329
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q47PU3"
FT HELIX 559..563
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 570..574
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 578..603
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 612..624
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 627..632
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 642..648
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 650..659
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 660..662
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 663..667
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 673..678
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 679..681
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 682..686
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 690..709
FT /evidence="ECO:0007829|PDB:6KJG"
FT STRAND 710..712
FT /evidence="ECO:0007829|PDB:6KJG"
FT STRAND 714..718
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 724..733
FT /evidence="ECO:0007829|PDB:6KJG"
FT STRAND 741..749
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 751..753
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 754..760
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 762..764
FT /evidence="ECO:0007829|PDB:6KJG"
FT TURN 765..767
FT /evidence="ECO:0007829|PDB:6KJG"
FT STRAND 768..772
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 780..782
FT /evidence="ECO:0007829|PDB:6KJG"
FT STRAND 789..796
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 798..800
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 804..814
FT /evidence="ECO:0007829|PDB:6KJG"
FT STRAND 815..828
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 831..837
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 841..844
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 847..849
FT /evidence="ECO:0007829|PDB:6KJG"
FT HELIX 859..868
FT /evidence="ECO:0007829|PDB:6KJG"
FT STRAND 875..880
FT /evidence="ECO:0007829|PDB:6KJG"
FT STRAND 888..895
FT /evidence="ECO:0007829|PDB:6KJG"
SQ SEQUENCE 905 AA; 101032 MW; B3ACE4152EAE7487 CRC64;
MTRIRPDYDA IVIGAGFSGV RSLWELRRLG LTARCFDAGS DVGGTWWWNR YPGCRTDGEA
WVYALKFLPE LLEEWDFTER YPPQEEIQWY LSRVLDRYDL RKDIEFNTEV KSAHYSDHDS
IWKITTASGK VATARYFLPA TGITSIPKEP PFPGLQSFKG EVYQTSTWPA HEIEFENKRI
GVIGTGSTGI QVITKLAPVA EQLIVFQRTP NYVIPAQNYP LDEKKREDIK KTFDATWDIA
KRNLAGHAVK HSGRMVASAG GPEEIQRVFE DGWARGCYDF QLGTFDDSFM DPHANAVTSD
FIRQKIRSIV RDGDTAEVLC PTYPFGARRP PCADGYYETF NRSNVKLVDI REDEIEVYDQ
GIKTASGAEY ELDMIILALG FDTGTGAMNK IDIRGSQNRS LRESWTRRLE TFAGVLVHGY
PNMFVVCGPH LPAGNQPVSL EAFASWIGKT IEHMETNGLA SIDVSNEAMD AWTTHVEQVW
GGSFLAKHAH EQGSWFVGTN IPGKPSRIMF YFGGMVNLEP WLIKELETGW SSMSFTRLDG
AEASNGVSKQ TVGGVHVTPE MLESVQIPLE ADKVGMTPAE KSKLVNAATA VYIDMAVEEM
RSRGLAPKAD YRVHWWKVMQ DFVDSGEGQR VLQETSLTNQ ELERVIAKLG IEGEVIARMG
PEIVNILTGK THALAHIMRD DLLFRVYLSD EGRRANRYMA EYARLLTSQR RDIRILEIGA
GTGGTTSEVL NLCSPNGESF CAEYMYTDLS PGFFNAAKTT LKKWESHLAF QVLNIEDDPA
GQGFKEHTYD LIIAANVIHA TARLTNTLSN VHKLLKPGGV FGLVELTRLT PFYNLTFGSL
SGWWAGVDEG RTESPLQSPQ QWNSLLKQTG FSGVDLAAYD LPGPERHSCL LLSTALSNSV
TTNGH
