PSOD_ASPFU
ID PSOD_ASPFU Reviewed; 518 AA.
AC Q4WB01;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Cytochrome P450 monooxygenase psoD {ECO:0000303|PubMed:24082142};
DE EC=1.-.-.- {ECO:0000269|PubMed:24939566};
DE AltName: Full=Pseurotin biosynthesis protein D {ECO:0000303|PubMed:24082142};
GN Name=psoD {ECO:0000303|PubMed:24082142}; ORFNames=AFUA_8G00560;
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 INDUCTION.
RX PubMed=21388144; DOI=10.1021/pr1012812;
RA Voedisch M., Scherlach K., Winkler R., Hertweck C., Braun H.P., Roth M.,
RA Haas H., Werner E.R., Brakhage A.A., Kniemeyer O.;
RT "Analysis of the Aspergillus fumigatus proteome reveals metabolic changes
RT and the activation of the pseurotin A biosynthesis gene cluster in response
RT to hypoxia.";
RL J. Proteome Res. 10:2508-2524(2011).
RN [3]
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 [4]
RP FUNCTION, 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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of pseurotin A, a competitive inhibitor of
CC chitin synthase and an inducer of nerve-cell proliferation
CC (PubMed:24082142, PubMed:24939566). The PKS-NRPS hybrid synthetase psoA
CC is responsible for the biosynthesis of azaspirene, one of the first
CC intermediates having the 1-oxa-7-azaspiro[4,4]-non-2-ene-4,6-dione core
CC of pseurotin, via condensation of one acetyl-CoA, 4 malonyl-CoA, and a
CC L-phenylalanine molecule (PubMed:24082142, PubMed:24939566). The dual-
CC functional monooxygenase/methyltransferase psoF seems to be involved in
CC the addition of the C3 methyl group onto the pseurotin scaffold
CC (PubMed:24939566). Azaspirene is then converted to synerazol through 4
CC steps including oxidation of C17 by the cytochrome P450 monooxygenase
CC psoD, O-methylation of the hydroxy group of C8 by the methyltransferase
CC psoC, and the trans-to-cis isomerization of the C13 olefin by the
CC glutathione S-transferase psoE (PubMed:24939566). The fourth step of
CC synerazol production is performed by the dual-functional
CC monooxygenase/methyltransferase psoF which seems to catalyze the
CC epoxidation of the intermediate deepoxy-synerazol (PubMed:24939566).
CC Synerazol can be attacked by a water molecule nonenzymatically at two
CC different positions to yield two diol products, pseurotin A and
CC pseurotin D (PubMed:24939566). {ECO:0000269|PubMed:24082142,
CC ECO:0000269|PubMed:24939566}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:24082142, ECO:0000269|PubMed:24939566}.
CC -!- INDUCTION: Expression is induced under hypoxic conditions
CC (PubMed:21388144). {ECO:0000269|PubMed:21388144}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of pseurotin
CC (PubMed:24082142, PubMed:24939566). {ECO:0000269|PubMed:24082142,
CC ECO:0000269|PubMed:24939566}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AAHF01000014; EAL85111.2; -; Genomic_DNA.
DR RefSeq; XP_747149.2; XM_742056.2.
DR AlphaFoldDB; Q4WB01; -.
DR SMR; Q4WB01; -.
DR STRING; 746128.CADAFUBP00008379; -.
DR PRIDE; Q4WB01; -.
DR EnsemblFungi; EAL85111; EAL85111; AFUA_8G00560.
DR GeneID; 3504508; -.
DR KEGG; afm:AFUA_8G00560; -.
DR eggNOG; KOG0156; Eukaryota.
DR HOGENOM; CLU_001570_2_1_1; -.
DR InParanoid; Q4WB01; -.
DR OMA; KAFIMNM; -.
DR OrthoDB; 702827at2759; -.
DR Proteomes; UP000002530; Chromosome 8.
DR GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0006694; P:steroid biosynthetic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..518
FT /note="Cytochrome P450 monooxygenase psoD"
FT /id="PRO_0000438198"
FT BINDING 442
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 518 AA; 59818 MW; B9E2DCD5BA3ED9FC CRC64;
MIISSYHLLA PRCRRDQKVY NKSIHVLNTV AKGIKGWPFL GSAPALAAVD TNGIIGIFKS
WAEQYGSITQ FSAMGDKQVI LTEDKDAREL FVRRGIKYSD RGAPHAVEYI SMKQNPGFRP
KDDGWRRQRS MIQSAINITS INKYQSLMDD EATFTVNALL QSPDSFHGEF LRYSYSVLTS
SLLGFSVRSP SDPFIHHNET FTAELMNSFR PDCFPSNVFP VLRKLPMWLL PSLRTMERLR
KEYVGEMWAF RRKIEKLVKE GSATECIYKH FLLHRDQYNV TEEESVHTFQ AMIDGGTRSP
HNNLLTFLFL MMEFPEWQKK LQEEVDRVVG RDRMPSYRDI PNLPTVRAIV KETVRYRSIV
AEMGIGHCLQ TDDIYKGYFF EKGTVFNAIF ASILMDKDTY PDGKLFNPAR WLEPSYPTYK
EPLTTYPNCQ GFPAFGYGRR ACPGVDFAER TLVIMFAKLG WTMNIRWPRD EDGNELREEL
QYEPVPAPRP LKFGCRLEAR DADRAKIVEE AAKHLKLQ
