ADAC_ASPNG
ID ADAC_ASPNG Reviewed; 414 AA.
AC G3KLH4;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=FAD-dependent monooxygenase adaC {ECO:0000303|PubMed:21866960};
DE EC=1.14.14.- {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=ATCC64974_92720;
OS Aspergillus niger.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=5061;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, CATALYTIC
RP ACTIVITY, AND PATHWAY.
RC STRAIN=ATCC 1015 / NV DSM 2061;
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).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 64974 / FGSC A733 / N402;
RX PubMed=30319579; DOI=10.3389/fmicb.2018.02269;
RA Laothanachareon T., Tamayo-Ramos J.A., Nijsse B., Schaap P.J.;
RT "Forward genetics by genome sequencing uncovers the central role of the
RT Aspergillus niger goxB locus in hydrogen peroxide induced glucose oxidase
RT expression.";
RL Front. Microbiol. 9:2269-2269(2018).
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; JN257714; AEN83887.1; -; Genomic_DNA.
DR EMBL; OGUI01000016; SPB51662.1; -; Genomic_DNA.
DR AlphaFoldDB; G3KLH4; -.
DR SMR; G3KLH4; -.
DR VEuPathDB; FungiDB:An11g07330; -.
DR VEuPathDB; FungiDB:ASPNIDRAFT2_1139199; -.
DR VEuPathDB; FungiDB:ATCC64974_92720; -.
DR VEuPathDB; FungiDB:M747DRAFT_298771; -.
DR OrthoDB; 1519546at2759; -.
DR Proteomes; UP000236662; 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 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT CHAIN 1..414
FT /note="FAD-dependent monooxygenase adaC"
FT /id="PRO_0000446347"
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; 45561 MW; 18980F105D1DC4E3 CRC64;
MTPPILIIGA GLSGLTISRI LTNASIPNIV FEASTPDRSQ GYAISLREWG YTSLLTALGD
LPLRSLTRGV APDRILGGTG WIDQALRDNH TGNLLVAPDP EAKQCIVRAN RNALRTWIAD
SGDEEVDIRY GHRLRSVQGS MGNVTATFDN 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
