APDD_EMENI
ID APDD_EMENI Reviewed; 624 AA.
AC Q5ATH0; C8VEB1;
DT 30-NOV-2016, 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 apdD {ECO:0000303|PubMed:17369821};
DE EC=1.-.-.- {ECO:0000305|PubMed:17369821};
DE AltName: Full=Aspyridones biosynthesis protein D {ECO:0000303|PubMed:17369821};
GN Name=apdD {ECO:0000303|PubMed:17369821}; ORFNames=AN8410;
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, INDUCTION, AND PATHWAY.
RX PubMed=17369821; DOI=10.1038/nchembio869;
RA Bergmann S., Schuemann J., Scherlach K., Lange C., Brakhage A.A.,
RA Hertweck C.;
RT "Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus
RT nidulans.";
RL Nat. Chem. Biol. 3:213-217(2007).
RN [4]
RP FUNCTION.
RX PubMed=20828130; DOI=10.1021/ja107084d;
RA Xu W., Cai X., Jung M.E., Tang Y.;
RT "Analysis of intact and dissected fungal polyketide synthase-nonribosomal
RT peptide synthetase in vitro and in Saccharomyces cerevisiae.";
RL J. Am. Chem. Soc. 132:13604-13607(2010).
RN [5]
RP FUNCTION.
RX DOI=10.1039/c3sc51785c;
RA Wasil Z., Pahirulzaman K.A.K., Butts C., Simpson T.J., Lazarus C.M.,
RA Cox R.J.;
RT "One pathway, many compounds: Heterologous expression of a fungal
RT biosynthetic pathway reveals its intrinsic potential for diversity.";
RL Chem. Sci. 4:3845-3856(2013).
RN [6]
RP FUNCTION.
RX PubMed=25494235; DOI=10.1021/ol503179v;
RA Zou Y., Xu W., Tsunematsu Y., Tang M., Watanabe K., Tang Y.;
RT "Methylation-dependent acyl transfer between polyketide synthase and
RT nonribosomal peptide synthetase modules in fungal natural product
RT biosynthesis.";
RL Org. Lett. 16:6390-6393(2014).
CC -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of aspyridones (PubMed:17369821, Ref.5). The
CC polyketide-amino acid backbone preaspyridone A is first assembled by
CC the PKS-NRPS hybrid apdA (PubMed:17369821, PubMed:20828130). The
CC assembly of preaspyridone A is initiated by loading of malonyl-CoA onto
CC apdA, followed by decarboxylation to yield the acetyl starter unit
CC (PubMed:20828130). The growing polyketide chain then elongates into a
CC tetraketide (PubMed:20828130). The adpA PKS module catalyzes three
CC Claisen condensations, as well as beta-keto processing and methylation
CC (PubMed:17369821, PubMed:20828130). Alpha-methylation step during
CC polyketide synthesis is a prerequisite and a key checkpoint for chain
CC transfer between PKS and NRPS modules (PubMed:25494235). The downstream
CC NRPS module contains the condensation (C), adenylation (A), and
CC thiolation (T) domains and catalyzes the incorporation of tyrosine via
CC the formation of the L-tyrosinyl-thioester and the amide linkage
CC between L-tyrosinyl-thioester and the tetraketide (PubMed:20828130).
CC The bimodular assembly line is terminated with a reductase (R) domain
CC that facilitates formation and release of the tetramic acid product
CC (PubMed:20828130). Because apdA lacks a designated enoylreductase (ER)
CC domain, the required activity is provided the enoyl reductase apdC
CC (PubMed:17369821, PubMed:20828130, Ref.5). ApdC appears to operate with
CC different stereoselectivity in different PKS cycle (Ref.5). Combined
CC with apdC, apdA is proposed to synthesize preaspyridone A via about 20
CC enzymatic steps (PubMed:20828130). A number of oxidative steps
CC performed successively by the cytochrome P450 monooxygenases apdE and
CC apdB are required for the conversion of preaspyridone A to aspyridone A
CC (PubMed:17369821). The cytochrome P450 monooxygenase apdE is
CC responsible for the oxidative dephenylation of preaspyridone A (Ref.5).
CC Finally, the predicted FAD-dependent monooxygenase apdD and the acyl-
CC CoA dehydrogenase apdG may be involved in the transformation of
CC aspyridone A into aspyridone B (PubMed:17369821) (Probable).
CC {ECO:0000269|PubMed:17369821, ECO:0000269|PubMed:20828130,
CC ECO:0000269|PubMed:25494235, ECO:0000269|Ref.5, ECO:0000305|Ref.5}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:17369821}.
CC -!- INDUCTION: Expression is positively regulated by the aspyridones
CC cluster specific transcription regulator apdR (PubMed:17369821).
CC {ECO:0000269|PubMed:17369821}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BN001305; CBF80483.1; -; Genomic_DNA.
DR EMBL; AACD01000153; EAA67032.1; -; Genomic_DNA.
DR RefSeq; XP_681679.1; XM_676587.1.
DR AlphaFoldDB; Q5ATH0; -.
DR SMR; Q5ATH0; -.
DR STRING; 162425.CADANIAP00002884; -.
DR PRIDE; Q5ATH0; -.
DR EnsemblFungi; CBF80483; CBF80483; ANIA_08410.
DR EnsemblFungi; EAA67032; EAA67032; AN8410.2.
DR GeneID; 2868841; -.
DR KEGG; ani:AN8410.2; -.
DR eggNOG; KOG3855; Eukaryota.
DR HOGENOM; CLU_009665_14_2_1; -.
DR InParanoid; Q5ATH0; -.
DR OMA; SMPSEPW; -.
DR OrthoDB; 366744at2759; -.
DR Proteomes; UP000000560; Chromosome V.
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; IEA:UniProt.
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..624
FT /note="FAD-dependent monooxygenase apdD"
FT /id="PRO_0000438454"
FT BINDING 74..75
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 187
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 359
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 369..373
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 624 AA; 68876 MW; 03E338459AD28020 CRC64;
MWSILSIKRS TSRMELMCLN AAECPINVFP EQQRNMPTES LNPGTVLIVG GGPVGLITAT
TLAKYGVRSV ILERNLTTTK WPKMDLTNSR SMEIYQRLGI ADALRNVAVP SHYPFTCLFS
SGLHADKAIT AWDLPSPDEY RRRIREQNDG SMPSEPWLRV SQEIFEAWLK ELGMENPLID
FRAGWKVKGA RELDHGVEVE AIHSDTGEVW KVSADFVIGC DGAHSAIRKS LEIPLDGGPI
HGYAVLVHFK SRDLSRIQKQ GQFWHLFFPN AASDGGSIKG AVIAQDEVDT WTVHRFMRPD
VDHTQLSSEE IVYDLLGGMG GQPFPIRIDE VLVRSTWTPS VALARSYAGP KHRIFIAGDA
CHQTVPTGGY GMNTGIADGY DIGWKLAAVI QGWAGPATLL SYEKERRPVG ELALQWSKVH
MGNLMKMSAE LGLDAHMIEL NNETGAELRG AMHSYLQTHD GHNQSIGVEM GYRYVSNICV
PGALDAELSP PEFHPRKYTP CTMPGYRAPH VYLTTGTPVS RLFGDGFTLV AFPEGEGLNA
STEQLREAAR KKALPLEVVE LPGEMHAHEV WGASLVLVRP DGFVSWHGDS VRSQEEADRI
IAQASGFDSE HLGNHVQAQE RSAL
