ID   PKFD_EMENI              Reviewed;         504 AA.
AC   Q5B8A3; A0A1U8QMZ3; C8VI79;
DT   13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT   26-APR-2005, sequence version 1.
DT   03-AUG-2022, entry version 107.
DE   RecName: Full=FAD-dependent monooxygenase pkfD {ECO:0000303|PubMed:23706169};
DE            EC=1.-.-.- {ECO:0000305|PubMed:23706169};
DE   AltName: Full=Aspernidine A biosynthesis cluster protein pkfD {ECO:0000303|PubMed:23706169};
GN   Name=pkfD {ECO:0000303|PubMed:23706169}; ORFNames=ANIA_03227;
OS   Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS   M139) (Aspergillus nidulans).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Nidulantes.
OX   NCBI_TaxID=227321;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=16372000; DOI=10.1038/nature04341;
RA   Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA   Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA   Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA   Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA   Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA   Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA   Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA   Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA   Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT   "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT   fumigatus and A. oryzae.";
RL   Nature 438:1105-1115(2005).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA   Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA   Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA   Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA   Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA   Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA   Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA   Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA   van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA   Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA   Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA   Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA   Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA   Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA   van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA   Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA   Oliver S.G., Turner G.;
RT   "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT   effort.";
RL   Fungal Genet. Biol. 46:S2-13(2009).
RN   [3]
RP   FUNCTION.
RX   PubMed=22510154; DOI=10.1021/ja3016395;
RA   Ahuja M., Chiang Y.M., Chang S.L., Praseuth M.B., Entwistle R.,
RA   Sanchez J.F., Lo H.C., Yeh H.H., Oakley B.R., Wang C.C.;
RT   "Illuminating the diversity of aromatic polyketide synthases in Aspergillus
RT   nidulans.";
RL   J. Am. Chem. Soc. 134:8212-8221(2012).
RN   [4]
RP   IDENTIFICATION, DISRUPTION PHENOTYPE, FUNCTION, AND PATHWAY.
RX   PubMed=23706169; DOI=10.1021/ol401187b;
RA   Yaegashi J., Praseuth M.B., Tyan S.W., Sanchez J.F., Entwistle R.,
RA   Chiang Y.M., Oakley B.R., Wang C.C.;
RT   "Molecular genetic characterization of the biosynthesis cluster of a
RT   prenylated isoindolinone alkaloid aspernidine A in Aspergillus nidulans.";
RL   Org. Lett. 15:2862-2865(2013).
RN   [5]
RP   INDUCTION.
RX   PubMed=25701285; DOI=10.1534/genetics.115.174342;
RA   Oiartzabal-Arano E., Garzia A., Gorostidi A., Ugalde U., Espeso E.A.,
RA   Etxebeste O.;
RT   "Beyond asexual development: modifications in the gene expression profile
RT   caused by the absence of the Aspergillus nidulans transcription factor
RT   FlbB.";
RL   Genetics 199:1127-1142(2015).
CC   -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC       mediates the biosynthesis of aspernidine A, a prenylated isoindolinone
CC       (PubMed:23706169). The starting point of the biosynthesis of aspernidin
CC       A is the production of orsellinaldehyde by the non-reducing polyketide
CC       synthase pkfA (PubMed:22510154). Hydroxylation, methylation of one of
CC       the phenol groups, and prenylation, presumably catalyzed by the
CC       prenyltransferase pkfE, would be needed to yield aspernidine D
CC       (Probable). Subsequently, the cytochrome P450 monooxygenase pkfB is
CC       responsible for hydroxylation of aspernidine D to yield aspernidine E
CC       (PubMed:23706169). The dehydrogenase pkfF may be responsible for
CC       further oxidation of aspernidine E to form a dialdehyde intermediate
CC       which is further transformed in a series of steps, some of which are
CC       enzyme-mediated, to generate aspernidine A (Probable). The possibility
CC       that additional enzymes outside of the cluster are involved in
CC       aspernidine A biosynthesis cannot be excluded (Probable).
CC       {ECO:0000269|PubMed:22510154, ECO:0000269|PubMed:23706169,
CC       ECO:0000305|PubMed:23706169}.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:23706169}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of Aspernidine A.
CC       {ECO:0000269|PubMed:23706169}.
CC   -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC       {ECO:0000305}.
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DR   EMBL; AACD01000054; EAA63128.1; -; Genomic_DNA.
DR   EMBL; BN001306; CBF83145.1; -; Genomic_DNA.
DR   RefSeq; XP_660831.1; XM_655739.1.
DR   AlphaFoldDB; Q5B8A3; -.
DR   SMR; Q5B8A3; -.
DR   STRING; 162425.CADANIAP00009835; -.
DR   EnsemblFungi; CBF83145; CBF83145; ANIA_03227.
DR   EnsemblFungi; EAA63128; EAA63128; AN3227.2.
DR   GeneID; 2874281; -.
DR   KEGG; ani:AN3227.2; -.
DR   eggNOG; KOG2614; Eukaryota.
DR   HOGENOM; CLU_009665_6_3_1; -.
DR   InParanoid; Q5B8A3; -.
DR   OMA; AHASFTH; -.
DR   OrthoDB; 521070at2759; -.
DR   Proteomes; UP000000560; Chromosome VI.
DR   Proteomes; UP000005890; Unassembled WGS sequence.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR002938; FAD-bd.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   Pfam; PF01494; FAD_binding_3; 1.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   2: Evidence at transcript level;
KW   FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Reference proteome.
FT   CHAIN           1..504
FT                   /note="FAD-dependent monooxygenase pkfD"
FT                   /id="PRO_0000446345"
FT   REGION          1..76
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..20
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        35..74
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         109..110
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         122
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         305..307
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         382
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
FT   BINDING         392..396
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:A6T923"
SQ   SEQUENCE   504 AA;  55079 MW;  68B1E4FF895F5B25 CRC64;
     MGSLWSSPSL LPSQQDNETE PFSHLPKEIG TDPTLREDSN VSNRNSEAAS TSTDSSTNTN
     ENHASTSQSS LEGAPDSGPI KIAIIGGGII GIITALGLIH RGINVTVYER APKYTETSAG
     FSFSKGARKA MEIVSPRVLE ALLRVAAPNK HPFIRYFDGF TPGADEAQWQ IPAERPDYYG
     CLRAAFLESL GQEVPEGIVK FGKVLESYED NEEGKVLLRF RDGSTAEVDA VIGCDGIKSR
     TRRIMLGDTH PAAAPGYTEI VAYRAVLPLE GVVAALGEDR GHSHCLAVGP DAYTVSYPIA
     NKPLANMILF RKQRGSWANS DKLLETCHRS TAQDAVKDWK PEIQRLVDLL PENPNKWAIF
     DTSDNPVPSY VSASGRVCIA GDAAHASTPF LASGAAMGVE DAAVLATVLN TALKEQSYNK
     TTVVKRKAIT AAFQAYSGIR MQRSQRVVKD SRTVGEVCMW QDAETARDPE KCFQAIWQRY
     TQIWEFDVEE MVERARSECV RLFS