AACUM_ASPA1
ID AACUM_ASPA1 Reviewed; 312 AA.
AC A0A1L9WLF1;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Atrochrysone carboxyl ACP thioesterase AacuM {ECO:0000250|UniProtKB:Q5BH31};
DE Short=ACTE AacuM {ECO:0000250|UniProtKB:Q5BH31};
DE EC=3.1.2.- {ECO:0000250|UniProtKB:Q5BH31};
DE AltName: Full=Secalonic acid biosynthesis cluster protein M {ECO:0000303|PubMed:30996871};
GN Name=AacuM {ECO:0000303|PubMed:30996871}; ORFNames=ASPACDRAFT_33688;
OS Aspergillus aculeatus (strain ATCC 16872 / CBS 172.66 / WB 5094).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=690307;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 16872 / CBS 172.66 / WB 5094;
RX PubMed=28196534; DOI=10.1186/s13059-017-1151-0;
RA de Vries R.P., Riley R., Wiebenga A., Aguilar-Osorio G., Amillis S.,
RA Uchima C.A., Anderluh G., Asadollahi M., Askin M., Barry K., Battaglia E.,
RA Bayram O., Benocci T., Braus-Stromeyer S.A., Caldana C., Canovas D.,
RA Cerqueira G.C., Chen F., Chen W., Choi C., Clum A., Dos Santos R.A.,
RA Damasio A.R., Diallinas G., Emri T., Fekete E., Flipphi M., Freyberg S.,
RA Gallo A., Gournas C., Habgood R., Hainaut M., Harispe M.L., Henrissat B.,
RA Hilden K.S., Hope R., Hossain A., Karabika E., Karaffa L., Karanyi Z.,
RA Krasevec N., Kuo A., Kusch H., LaButti K., Lagendijk E.L., Lapidus A.,
RA Levasseur A., Lindquist E., Lipzen A., Logrieco A.F., MacCabe A.,
RA Maekelae M.R., Malavazi I., Melin P., Meyer V., Mielnichuk N., Miskei M.,
RA Molnar A.P., Mule G., Ngan C.Y., Orejas M., Orosz E., Ouedraogo J.P.,
RA Overkamp K.M., Park H.-S., Perrone G., Piumi F., Punt P.J., Ram A.F.,
RA Ramon A., Rauscher S., Record E., Riano-Pachon D.M., Robert V., Roehrig J.,
RA Ruller R., Salamov A., Salih N.S., Samson R.A., Sandor E., Sanguinetti M.,
RA Schuetze T., Sepcic K., Shelest E., Sherlock G., Sophianopoulou V.,
RA Squina F.M., Sun H., Susca A., Todd R.B., Tsang A., Unkles S.E.,
RA van de Wiele N., van Rossen-Uffink D., Oliveira J.V., Vesth T.C.,
RA Visser J., Yu J.-H., Zhou M., Andersen M.R., Archer D.B., Baker S.E.,
RA Benoit I., Brakhage A.A., Braus G.H., Fischer R., Frisvad J.C.,
RA Goldman G.H., Houbraken J., Oakley B., Pocsi I., Scazzocchio C.,
RA Seiboth B., vanKuyk P.A., Wortman J., Dyer P.S., Grigoriev I.V.;
RT "Comparative genomics reveals high biological diversity and specific
RT adaptations in the industrially and medically important fungal genus
RT Aspergillus.";
RL Genome Biol. 18:RESEARCH28.1-RESEARCH28.45(2017).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=28253713; DOI=10.4149/neo_2017_304;
RA Gao X., Sun H.L., Liu D.S., Zhang J.R., Zhang J., Yan M.M., Pan X.H.;
RT "Secalonic acid- F inhibited cell growth more effectively than 5-
RT fluorouracil on hepatocellular carcinoma in vitro and in vivo.";
RL Neoplasma 64:344-350(2017).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=29248948; DOI=10.1007/s00284-017-1411-y;
RA Yodsing N., Lekphrom R., Sangsopha W., Aimi T., Boonlue S.;
RT "Secondary Metabolites and Their Biological Activity from Aspergillus
RT aculeatus KKU-CT2.";
RL Curr. Microbiol. 75:513-518(2018).
RN [4]
RP IDENTIFICATION, AND FUNCTION.
RX PubMed=30996871; DOI=10.1039/c8sc05126g;
RA Greco C., de Mattos-Shipley K., Bailey A.M., Mulholland N.P., Vincent J.L.,
RA Willis C.L., Cox R.J., Simpson T.J.;
RT "Structure revision of cryptosporioptides and determination of the genetic
RT basis for dimeric xanthone biosynthesis in fungi.";
RL Chem. Sci. 10:2930-2939(2019).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=30678274; DOI=10.3390/molecules24030393;
RA Xie L., Li M., Liu D., Wang X., Wang P., Dai H., Yang W., Liu W., Hu X.,
RA Zhao M.;
RT "Secalonic Acid-F, a Novel Mycotoxin, Represses the Progression of
RT Hepatocellular Carcinoma via MARCH1 Regulation of the PI3K/AKT/beta-catenin
RT Signaling Pathway.";
RL Molecules 24:0-0(2019).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=33015446; DOI=10.1021/acsomega.0c02505;
RA Farooq S., Qayum A., Nalli Y., Lauro G., Chini M.G., Bifulco G.,
RA Chaubey A., Singh S.K., Riyaz-Ul-Hassan S., Ali A.;
RT "Discovery of a Secalonic Acid Derivative from Aspergillus aculeatus, an
RT Endophyte of Rosa damascena Mill., Triggers Apoptosis in MDA-MB-231 Triple
RT Negative Breast Cancer Cells.";
RL ACS Omega 5:24296-24310(2020).
RN [7]
RP FUNCTION, AND PATHWAY.
RX PubMed=33891392; DOI=10.1021/acs.jnatprod.1c00022;
RA Wei X., Chen X., Chen L., Yan D., Wang W.G., Matsuda Y.;
RT "Heterologous biosynthesis of tetrahydroxanthone dimers: determination of
RT key factors for selective or divergent synthesis.";
RL J. Nat. Prod. 84:1544-1549(2021).
CC -!- FUNCTION: Atrochrysone carboxyl ACP thioesterase; part of the gene
CC cluster that mediates the biosynthesis of the tetrahydroxanthone dimer
CC secalonic acid D (PubMed:30996871, PubMed:33891392). The pathway begins
CC with the synthesis of atrochrysone thioester by the polyketide synthase
CC AacuL (Probable). The atrochrysone carboxyl ACP thioesterase AacuM then
CC breaks the thioester bond and releases the atrochrysone carboxylic acid
CC from AacuL (Probable). Atrochrysone carboxylic acid is decarboxylated
CC by the decarboxylase AacuI, and oxidized by the anthrone oxygenase
CC AacuG to yield emodin (Probable). Emodin is then reduced to emodin
CC hydroquinone by a yet unidentified oxidoreductase (Probable). A-ring
CC reduction by the short chain dehydrogenase AacuN, dehydration by the
CC scytalone dehydratase-like protein AacuK and probable spontaneous re-
CC oxidation, results in overall deoxygenation to chrysophanol
CC (PubMed:33891392). Baeyer-Villiger oxidation by the Baeyer-Villiger
CC monooxygenase (BVMO) AacuH then yields monodictyphenone
CC (PubMed:33891392). Monodictyphenone is transformed into compounds with
CC the tetrahydroxanthone skeleton via methylesterification by the
CC methyltransferase AacuQ, followed by the action of the flavin-dependent
CC monooxygenase AacuC, the isomerase AacuP, and the short chain
CC dehydrogenase/reductase AacuF or AacuD (PubMed:33891392). AacuF and
CC AacuD should accept the same compound as a substrate but perform the
CC ketoreduction with a different stereoselectivity, thus yielding
CC blennolides B and A, respectively (PubMed:33891392). In the final step
CC of the biosynthesis, the cytochrome P450 monooxygenase AacuE accepts
CC blennolide B and/or blennolide A to conduct the dimerization reaction
CC to furnish the tetrahydroxanthone dimers, secalonic acids D, B, and F
CC (PubMed:33891392). {ECO:0000269|PubMed:30996871,
CC ECO:0000269|PubMed:33891392, ECO:0000305|PubMed:33891392}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=atrochrysone carboxyl-[ACP] + H2O = atrochrysone carboxylate +
CC H(+) + holo-[ACP]; Xref=Rhea:RHEA:64236, Rhea:RHEA-COMP:9685,
CC Rhea:RHEA-COMP:16552, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:149712, ChEBI:CHEBI:149713;
CC Evidence={ECO:0000250|UniProtKB:Q5BH31};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64237;
CC Evidence={ECO:0000250|UniProtKB:Q5BH31};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q988B9};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q988B9};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:30996871}.
CC -!- BIOTECHNOLOGY: Secalonic acids show unprecedented anticancer activities
CC against various human cancer cells and might be interesting for further
CC derivatization, targeting diseases such as cancer.
CC {ECO:0000269|PubMed:28253713, ECO:0000269|PubMed:29248948,
CC ECO:0000269|PubMed:30678274, ECO:0000269|PubMed:33015446}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC {ECO:0000305}.
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DR EMBL; KV878984; OJJ96971.1; -; Genomic_DNA.
DR RefSeq; XP_020053311.1; XM_020199981.1.
DR SMR; A0A1L9WLF1; -.
DR STRING; 690307.A0A1L9WLF1; -.
DR EnsemblFungi; OJJ96971; OJJ96971; ASPACDRAFT_33688.
DR GeneID; 30973795; -.
DR VEuPathDB; FungiDB:ASPACDRAFT_33688; -.
DR OrthoDB; 576967at2759; -.
DR Proteomes; UP000184546; Unassembled WGS sequence.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF00753; Lactamase_B; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..312
FT /note="Atrochrysone carboxyl ACP thioesterase AacuM"
FT /id="PRO_0000453431"
FT ACT_SITE 107
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255"
FT BINDING 103
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 108
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
SQ SEQUENCE 312 AA; 34766 MW; 13A86B161887CD50 CRC64;
MGEGGYRQIN KTLNVCAFDD YLVTQQSRLP KLLDIEQLSP RVLRVLGQNA GKFTLQGTNT
YIVGTGQHRL IIDTAQGYRE WADLIDVTLS NRSISLSHVF LTHWHGDHTG GVPDLIRMYP
HLADGIYKNS PEQGQHPIEE GQIFKVEGAT IRAVHGPGHS HDHMCFVLEE ENAMFTGDNV
LGHGTSAVEQ LGLYMDTLRK LQAQGCRTGY PAHGAVIPDL NLKIATELAQ KTRREKQCLA
ALGRIRKERP TGQLASVTVG ELIDVVHGTR VNEEVRKMAL EPFMEEVLRK LAEDGKVAFR
VRKGVKTWFA LT
