ADAD_ASPNC
ID ADAD_ASPNC Reviewed; 249 AA.
AC A2QX25;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=O-methyltransferase adaD {ECO:0000303|PubMed:21866960};
DE EC=2.1.1.- {ECO:0000269|PubMed:21866960};
DE AltName: Full=2-acetyl-2-decarboxamidoanthrotainin biosynthesis cluster protein D {ECO:0000303|PubMed:21866960};
GN Name=adaD {ECO:0000303|PubMed:21866960}; ORFNames=An11g07340;
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: O-methyltransferase; part of the gene cluster that mediates
CC the biosynthesis of the linear tetracyclic TAN-1612 neuropeptide Y
CC receptor antagonist (PubMed:21866960). The decaketide backbone of TAN-
CC 1612 is synthesized by the non-reducing polyketide synthase adaA via
CC condensation of one acetyl-CoA starter unit with 9 malonyl-CoA units.
CC The FAD-dependent monooxygenase adaC then performs hydroxylation at C2
CC while the polaketide chain is still attached to the NRPKS adaA
CC (PubMed:21866960). The alpha-hydroxylation step at C2 appears to be
CC crucial for the following C18-C1 Claisen cyclization and release of the
CC C9-hydroxyl version of TAN-1612 from the NRPKS adaA, two steps
CC 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=2-acetyl-3,4a,8,10,11,12a-hexahydroxy-1,4,4a,5,12,12a-
CC hexahydrotetracene-1,12-dione + S-adenosyl-L-methionine = H(+) + S-
CC adenosyl-L-homocysteine + TAN-1612; Xref=Rhea:RHEA:64100,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:146217, ChEBI:CHEBI:146218;
CC Evidence={ECO:0000269|PubMed:21866960};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64101;
CC Evidence={ECO:0000269|PubMed:21866960};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:21866960}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000255}.
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DR EMBL; AM270243; CAK40781.1; -; Genomic_DNA.
DR RefSeq; XP_001394708.1; XM_001394671.1.
DR AlphaFoldDB; A2QX25; -.
DR PaxDb; A2QX25; -.
DR EnsemblFungi; CAK40781; CAK40781; An11g07340.
DR GeneID; 4984954; -.
DR KEGG; ang:ANI_1_2246094; -.
DR VEuPathDB; FungiDB:An11g07340; -.
DR HOGENOM; CLU_046029_0_0_1; -.
DR Proteomes; UP000006706; Chromosome 7R.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016584; MeTrfase_VrtF.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR PIRSF; PIRSF011491; Mtase_YbcY_prd; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Reference proteome; Transferase.
FT CHAIN 1..249
FT /note="O-methyltransferase adaD"
FT /id="PRO_0000446348"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 249 AA; 28304 MW; 534F5B43E321E020 CRC64;
MSSVTLTTTT TTTSTPPKPT PKDEPQEQIY TPWRLFIYDI WVLGIVSTLA WGCRISTYLI
PLFRSNVGKK HLDIGAGTGY YLNQARIPST TQLTIVDNET HALNVALARC KHPSTQTHGI
VTDILQPSPF PETYLTNNDK KFDSVSMYYL LHCLPVPVAS KCKIFTHLKK YMTEDGVVHG
ANVLGKGVRK DNWFARIIRR GCLNHGVFHN EEDNAYEFER ALRENFWEVE TWVVGSVFVF
RAKRPILDA
