ID   AZAD_ASPNA              Reviewed;         461 AA.
AC   G3XMB8;
DT   02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT   14-DEC-2011, sequence version 1.
DT   03-AUG-2022, entry version 33.
DE   RecName: Full=O-acetyltransferase azaD {ECO:0000303|PubMed:22921072};
DE            EC=2.3.1.- {ECO:0000305|PubMed:22921072};
DE   AltName: Full=Azaphilone biosynthesis cluster protein azaD {ECO:0000303|PubMed:22921072};
GN   Name=azaD {ECO:0000303|PubMed:22921072}; ORFNames=ASPNIDRAFT_189181;
OS   Aspergillus niger (strain ATCC 1015 / CBS 113.46 / FGSC A1144 / LSHB Ac4 /
OS   NCTC 3858a / NRRL 328 / USDA 3528.7).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=380704;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 1015 / CBS 113.46 / FGSC A1144 / LSHB Ac4 / NCTC 3858a / NRRL
RC   328 / USDA 3528.7;
RX   PubMed=21543515; DOI=10.1101/gr.112169.110;
RA   Andersen M.R., Salazar M.P., Schaap P.J., van de Vondervoort P.J.I.,
RA   Culley D., Thykaer J., Frisvad J.C., Nielsen K.F., Albang R., Albermann K.,
RA   Berka R.M., Braus G.H., Braus-Stromeyer S.A., Corrochano L.M., Dai Z.,
RA   van Dijck P.W.M., Hofmann G., Lasure L.L., Magnuson J.K., Menke H.,
RA   Meijer M., Meijer S.L., Nielsen J.B., Nielsen M.L., van Ooyen A.J.J.,
RA   Pel H.J., Poulsen L., Samson R.A., Stam H., Tsang A., van den Brink J.M.,
RA   Atkins A., Aerts A., Shapiro H., Pangilinan J., Salamov A., Lou Y.,
RA   Lindquist E., Lucas S., Grimwood J., Grigoriev I.V., Kubicek C.P.,
RA   Martinez D., van Peij N.N.M.E., Roubos J.A., Nielsen J., Baker S.E.;
RT   "Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015
RT   versus enzyme-producing CBS 513.88.";
RL   Genome Res. 21:885-897(2011).
RN   [2]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=22921072; DOI=10.1016/j.chembiol.2012.07.004;
RA   Zabala A.O., Xu W., Chooi Y.H., Tang Y.;
RT   "Characterization of a silent azaphilone gene cluster from Aspergillus
RT   niger ATCC 1015 reveals a hydroxylation-mediated pyran-ring formation.";
RL   Chem. Biol. 19:1049-1059(2012).
CC   -!- FUNCTION: O-acetyltransferase; part of the gene cluster that mediates
CC       the biosynthesis of azaphilones, a class of fungal metabolites
CC       characterized by a highly oxygenated pyrano-quinone bicyclic core and
CC       exhibiting a broad range of bioactivities (PubMed:22921072). In the
CC       first step, the non-reducing polyketide synthase azaA forms the
CC       hexaketide precursor from successive condensations of five malonyl-CoA
CC       units, presumably with a simple acetyl-CoA starter unit
CC       (PubMed:22921072). The reactive polyketide chain then undergoes a PT-
CC       mediated C2-C7 cyclization to afford the aromatic ring and is
CC       eventually released as an aldehyde through the R-domain
CC       (PubMed:22921072). The putative ketoreductase azaE is proposed to
CC       catalyze the reduction of the terminal ketone resulting in the early
CC       culture product FK17-P2a (PubMed:22921072). The monooxygenase azaH was
CC       demonstrated to be the only enzyme required to convert FK17-P2a to
CC       azanigerone E (PubMed:22921072). AzaH first hydroxylates the
CC       benzaldehyde intermediate FK17-P2a at C4, which triggers the formation
CC       of the pyran-ring to afford azanigerone E (PubMed:22921072). In
CC       parallel, the 2,4-dimethylhexanoyl chain is synthesized by the HR-PKS
CC       azaB and is proposed to be transferred to the C4-hydroxyl of
CC       azanigerone E by the acyltransferase azaD directly from the ACP domain
CC       of azaB (PubMed:22921072). Alternatively, the 2,4-dimethyl-hexanoyl
CC       chain may be offloaded from the HR-PKS as a carboxylic acid and
CC       converted to an acyl-CoA by azaF (PubMed:22921072). The resulting acyl-
CC       CoA molecule could then be taken up as a substrate by AzaD to form
CC       azanigerone B (PubMed:22921072). To yield the carboxylic acid
CC       substituent in azanigerone A, the hydroxypropyl side chain of
CC       azanigerone B would need to undergo a C-C oxidative cleavage catalyzed
CC       by cytochrome P450 AzaI (PubMed:22921072). AzaI is proposed to act on a
CC       vicinal diol that leads to a C-C bond scission either through an
CC       alkoxyradical intermediate or a peroxy complex (PubMed:22921072). In
CC       the biosynthesis of azanigerone A, azanigerone B first undergoes
CC       hydroxylation at C10, possibly catalyzed by one of the two FAD-
CC       dependent monooxygenases encoded in the cluster, azaG or azaL,
CC       resulting in the vicinal diol azanigerone C (PubMed:22921072).
CC       Oxidative cleavage of azanigerone C by azaI would yield the
CC       corresponding aldehyde derivative of azanigerone A (PubMed:22921072).
CC       Finally, the dehydrogenase azaJ is proposed to convert the aldehyde
CC       functional group into the carboxylic acid, completing the conversion
CC       from azanigerone B to azanigerone A (PubMed:22921072). Alternatively,
CC       the oxidation of aldehyde to carboxylic acid may be catalyzed by the
CC       same P450 enzyme azaI via consecutive oxidation or by endogenous
CC       alcohol dehydrogenase (PubMed:22921072). {ECO:0000269|PubMed:22921072}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:22921072}.
CC   -!- INDUCTION: Expression is under the control of the azaphilone cluster-
CC       specific transcription factor azaR (PubMed:22921072).
CC       {ECO:0000269|PubMed:22921072}.
CC   -!- SIMILARITY: Belongs to the trichothecene 3-O-acetyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; ACJE01000001; EHA28231.1; -; Genomic_DNA.
DR   AlphaFoldDB; G3XMB8; -.
DR   SMR; G3XMB8; -.
DR   EnsemblFungi; EHA28231; EHA28231; ASPNIDRAFT_189181.
DR   VEuPathDB; FungiDB:ASPNIDRAFT2_1114645; -.
DR   HOGENOM; CLU_026450_5_0_1; -.
DR   Proteomes; UP000009038; Unassembled WGS sequence.
DR   GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.559.10; -; 2.
DR   InterPro; IPR023213; CAT-like_dom_sf.
PE   2: Evidence at transcript level;
KW   Acyltransferase; Reference proteome; Transferase.
FT   CHAIN           1..461
FT                   /note="O-acetyltransferase azaD"
FT                   /id="PRO_0000437611"
SQ   SEQUENCE   461 AA;  52200 MW;  474C2D9BF789D0DB CRC64;
     MATNGFRPEY EDLGRYEDIL GQLPMLQVYS HIMLPFAMPE GLSQDTIIAD LEAAVRQIRA
     HVPWMAGKVV NVGKGPDNSG RYIVVPCPPP DPLIVVRDVT HAFPPYKEIQ RLKAPNSMLD
     SRLLAPTNAF PQRFEDSEED PFRVIRLQAS FVDGGVFLDF VTQHNMTDAG GLFGFARLVA
     MAMRGEQFSD SLLEQVNRDR RNIIPLLTPD EPMLDHSHHI RPPITDAQPV VRPDPARWHF
     LRFTAAKLAE LKDLASQTMT PDPEVPYITT DDAVSAFCWK KYITVRHRRR NTPDARSRFS
     RAMDGRKVLG IPAEYMGDLV HNVTTWLTFR ELVDLPLGEI ARHMRRELNR ANTAYHVRSF
     ATFIAQEPDK STIAYGGRFN PDTDVGSSSV LRVDLFPVFG KLGRPDFIRR PNFPGIPFPS
     LLYFFPQNPQ GECDSLTCLT DADMEALNQD SEWTSMVEYI G