APDC_EMENI
ID APDC_EMENI Reviewed; 333 AA.
AC Q5ATH1; C8VEB0;
DT 30-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Trans-enoyl reductase apdC {ECO:0000303|PubMed:17369821};
DE EC=1.-.-.- {ECO:0000305|PubMed:17369821};
DE AltName: Full=Aspyridones biosynthesis protein C {ECO:0000303|PubMed:17369821};
GN Name=apdC {ECO:0000303|PubMed:17369821}; ORFNames=AN8409;
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, CATALYTIC ACTIVITY, AND PATHWAY.
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, CATALYTIC ACTIVITY, AND PATHWAY.
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: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of aspyridones (PubMed:17369821, PubMed:20828130,
CC Ref.5). The polyketide-amino acid backbone preaspyridone A is first
CC assembled by the PKS-NRPS hybrid apdA (PubMed:17369821,
CC PubMed:20828130). The assembly of preaspyridone A is initiated by
CC loading of malonyl-CoA onto apdA, followed by decarboxylation to yield
CC the acetyl starter unit (PubMed:20828130). The growing polyketide chain
CC then elongates into a tetraketide (PubMed:20828130). The adpA PKS
CC module catalyzes three Claisen condensations, as well as beta-keto
CC processing and methylation (PubMed:17369821, PubMed:20828130). Alpha-
CC methylation step during polyketide synthesis is a prerequisite and a
CC key checkpoint for chain transfer between PKS and NRPS modules
CC (PubMed:25494235). The downstream NRPS module contains the condensation
CC (C), adenylation (A), and thiolation (T) domains and catalyzes the
CC incorporation of tyrosine via the formation of the L-tyrosinyl-
CC thioester and the amide linkage between L-tyrosinyl-thioester and the
CC tetraketide (PubMed:20828130). The bimodular assembly line is
CC terminated with a reductase (R) domain that facilitates formation and
CC release of the tetramic acid product (PubMed:20828130). Because apdA
CC lacks a designated enoylreductase (ER) domain, the required activity is
CC provided the enoyl reductase apdC (PubMed:17369821, PubMed:20828130,
CC Ref.5). ApdC appears to operate with different stereoselectivity in
CC different PKS cycle (Ref.5). Combined with apdC, apdA is proposed to
CC synthesize preaspyridone A via about 20 enzymatic steps
CC (PubMed:20828130). A number of oxidative steps performed successively
CC by the cytochrome P450 monooxygenases apdE and apdB are required for
CC the conversion of preaspyridone A to aspyridone A (PubMed:17369821).
CC The cytochrome P450 monooxygenase apdE is responsible for the oxidative
CC dephenylation of preaspyridone A (Ref.5). Finally, the predicted FAD-
CC dependent monooxygenase apdD and the acyl-CoA dehydrogenase apdG may be
CC involved in the transformation of aspyridone A into aspyridone B
CC (PubMed:17369821) (Probable). {ECO:0000269|PubMed:17369821,
CC ECO:0000269|PubMed:20828130, ECO:0000269|PubMed:25494235,
CC ECO:0000269|Ref.5, ECO:0000305|Ref.5}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:17369821, ECO:0000269|PubMed:20828130,
CC ECO:0000269|Ref.5}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
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 zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; BN001305; CBF80481.1; -; Genomic_DNA.
DR EMBL; AACD01000153; EAA67031.1; -; Genomic_DNA.
DR RefSeq; XP_681678.1; XM_676586.1.
DR AlphaFoldDB; Q5ATH1; -.
DR SMR; Q5ATH1; -.
DR STRING; 162425.CADANIAP00002883; -.
DR EnsemblFungi; CBF80481; CBF80481; ANIA_08409.
DR EnsemblFungi; EAA67031; EAA67031; AN8409.2.
DR GeneID; 2868866; -.
DR KEGG; ani:AN8409.2; -.
DR eggNOG; KOG1198; Eukaryota.
DR HOGENOM; CLU_026673_16_1_1; -.
DR InParanoid; Q5ATH1; -.
DR OMA; PARLVWH; -.
DR OrthoDB; 727365at2759; -.
DR Proteomes; UP000000560; Chromosome V.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NADP; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..333
FT /note="Trans-enoyl reductase apdC"
FT /id="PRO_0000438444"
FT BINDING 45..48
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 131..138
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 167..170
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 185
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 232..233
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 252..256
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 321..322
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 333 AA; 36095 MW; 0BDEAA58198EBB97 CRC64;
MIPPKQQTAL KITPEGRIAA VSSPLPSLQD NELLVCVKSI ALNPFDAKSA EMSPTIGATL
GCDFAGKIVA TGSNANDFNF SIGDRVCGCV FGNNPNRLDN GAFAEYVAVP ADLLLRIPEH
MDYNEAATLG VGLATVGMSL YHCLRLPMKP EQAGKSPSGY AAITTCSPHN FNLVKSLGAT
AAFDYHSPTC GRQIRDFSSG NLWYALDCIT DTRSMAVCYE AIGPSGGRYL SLDPFPIRGH
TRRSVKPNWV LSVTMYNQPI PWKRPFKRDA CPQDLEFAKS WFQIAQRMID AGEIRPHTSD
VKAGGWNGIP GGLELLQKGE VSGRKLVYEV ASH
