ADAC_ASPNC
ID ADAC_ASPNC Reviewed; 414 AA.
AC A2QX24;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=FAD-dependent monooxygenase adaC {ECO:0000303|PubMed:21866960};
DE EC=1.-.-.- {ECO:0000269|PubMed:21866960};
DE AltName: Full=2-acetyl-2-decarboxamidoanthrotainin biosynthesis cluster protein C {ECO:0000303|PubMed:21866960};
GN Name=adaC {ECO:0000303|PubMed:21866960}; ORFNames=An11g07330;
OS Aspergillus niger (strain CBS 513.88 / FGSC A1513).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=425011;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
RX PubMed=17259976; DOI=10.1038/nbt1282;
RA Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT niger CBS 513.88.";
RL Nat. Biotechnol. 25:221-231(2007).
RN [2]
RP IDENTIFICATION, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=21866960; DOI=10.1021/ja206906d;
RA Li Y., Chooi Y.H., Sheng Y., Valentine J.S., Tang Y.;
RT "Comparative characterization of fungal anthracenone and naphthacenedione
RT biosynthetic pathways reveals an alpha-hydroxylation-dependent Claisen-like
RT cyclization catalyzed by a dimanganese thioesterase.";
RL J. Am. Chem. Soc. 133:15773-15785(2011).
CC -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the linear tetracyclic TAN-1612
CC neuropeptide Y receptor antagonist (PubMed:21866960). The decaketide
CC backbone of TAN-1612 is synthesized by the non-reducing polyketide
CC synthase adaA via condensation of one acetyl-CoA starter unit with 9
CC malonyl-CoA units. The FAD-dependent monooxygenase adaC then performs
CC hydroxylation at C2 while the polaketide chain is still attached to the
CC NRPKS adaA (PubMed:21866960). The alpha-hydroxylation step at C2
CC appears to be crucial for the following C18-C1 Claisen cyclization and
CC release of the C9-hydroxyl version of TAN-1612 from the NRPKS adaA, two
CC steps performed by the lactamase-like protein adaB (PubMed:21866960).
CC Finally, the O-methyltransferase adaD performs the C9 O-methylation to
CC complete the biosynthesis of TAN-1612 (PubMed:21866960).
CC {ECO:0000269|PubMed:21866960}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(2,4-dioxopentyl)-3,6,8,9-tetrahydroxy-1-oxo-1,2,3,4-
CC tetrahydroanthracene-2-carboxyl-[ACP] + H(+) + NADPH + O2 = 3-(2,4-
CC dioxopentyl)-2,3,6,8,9-pentahydroxy-1-oxo-1,2,3,4-
CC tetrahydroanthracene-2-carboxyl-[ACP] + H2O + NADP(+);
CC Xref=Rhea:RHEA:64092, Rhea:RHEA-COMP:16518, Rhea:RHEA-COMP:16520,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:149687,
CC ChEBI:CHEBI:149688; Evidence={ECO:0000269|PubMed:21866960};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64093;
CC Evidence={ECO:0000269|PubMed:21866960};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:21866960}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; AM270243; CAK40780.1; -; Genomic_DNA.
DR RefSeq; XP_001394707.1; XM_001394670.2.
DR AlphaFoldDB; A2QX24; -.
DR SMR; A2QX24; -.
DR PaxDb; A2QX24; -.
DR EnsemblFungi; CAK40780; CAK40780; An11g07330.
DR GeneID; 4984953; -.
DR KEGG; ang:ANI_1_968094; -.
DR VEuPathDB; FungiDB:An11g07330; -.
DR HOGENOM; CLU_040697_0_0_1; -.
DR Proteomes; UP000006706; Chromosome 7R.
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 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase; Reference proteome.
FT CHAIN 1..414
FT /note="FAD-dependent monooxygenase adaC"
FT /id="PRO_0000446346"
FT BINDING 32..33
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 45
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 232..234
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 318..322
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 414 AA; 45547 MW; 8A1455FD2ED0E614 CRC64;
MTPPILIIGA GLSGLTVSRI LTNASIPNIV FEASTPDRSQ GYAISLRDWG YTSLLTALGD
LPLRSLTRGV APDRILGGTG WIDQALRDNH TGNLLVAPDP EAKQCIVRAN RNALRTWIAD
SGDEEVDIRY GHRLRSVQGS MGNVTATFEN GAKYQGSLVI AADGVHSSVR SQILPHVSPD
IVPVVVYHGE LELPRKEFDN LIRPHSGPSN ILAGVGDGFN TPITVCNITP THVHLDWSYS
RPSTENKENK DPLYRPHVSA AEAKQIPPAL LEEIASRDLA RPWSQLLNAE ALPTHRVFNW
VSRCVSVTRE DVNAAQKQGV VFIGDSWHAM PIFGGEGGNH ALVDAVELAE ALTGKEGNLD
AAVTGYYDRA WRRCQEAVRR SRQRFFQLHR PMREWMEIAE KKKMMAAMKG VEAH
