ARMP4_ARMGA
ID ARMP4_ARMGA Reviewed; 518 AA.
AC A0A2H3CNS9;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2018, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Cytochrome P450 monooxygenase ARMGADRAFT_1018417;
DE EC=1.-.-.-;
DE AltName: Full=Melleolide biosynthesis cluster protein ARMGADRAFT_1018417;
GN ORFNames=ARMGADRAFT_1018417;
OS Armillaria gallica (Bulbous honey fungus) (Armillaria bulbosa).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Physalacriaceae; Armillaria.
OX NCBI_TaxID=47427;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Ar21-2;
RX PubMed=29085064; DOI=10.1038/s41559-017-0347-8;
RA Sipos G., Prasanna A.N., Walter M.C., O'Connor E., Balint B., Krizsan K.,
RA Kiss B., Hess J., Varga T., Slot J., Riley R., Boka B., Rigling D.,
RA Barry K., Lee J., Mihaltcheva S., LaButti K., Lipzen A., Waldron R.,
RA Moloney N.M., Sperisen C., Kredics L., Vagvoelgyi C., Patrignani A.,
RA Fitzpatrick D., Nagy I., Doyle S., Anderson J.B., Grigoriev I.V.,
RA Gueldener U., Muensterkoetter M., Nagy L.G.;
RT "Genome expansion and lineage-specific genetic innovations in the forest
RT pathogenic fungi Armillaria.";
RL Nat. Ecol. Evol. 1:1931-1941(2017).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=21376582; DOI=10.1016/j.bmcl.2011.02.026;
RA Bohnert M., Miethbauer S., Dahse H.M., Ziemen J., Nett M., Hoffmeister D.;
RT "In vitro cytotoxicity of melleolide antibiotics: structural and
RT mechanistic aspects.";
RL Bioorg. Med. Chem. Lett. 21:2003-2006(2011).
RN [3]
RP FUNCTION.
RC STRAIN=FU02472;
RX PubMed=21148562; DOI=10.1074/jbc.m110.165845;
RA Engels B., Heinig U., Grothe T., Stadler M., Jennewein S.;
RT "Cloning and characterization of an Armillaria gallica cDNA encoding
RT protoilludene synthase, which catalyzes the first committed step in the
RT synthesis of antimicrobial melleolides.";
RL J. Biol. Chem. 286:6871-6878(2011).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=23864890; DOI=10.1155/2013/459271;
RA Chi C.W., Chen C.C., Chen Y.J.;
RT "Therapeutic and radiosensitizing effects of armillaridin on human
RT esophageal cancer cells.";
RL Evid. Based Complement Alternat. Med. 2013:459271-459271(2013).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=25746621; DOI=10.1615/intjmedmushrooms.v17.i2.70;
RA Liu T.P., Chen C.C., Shiao P.Y., Shieh H.R., Chen Y.Y., Chen Y.J.;
RT "Armillaridin, a honey medicinal mushroom, Armillaria mellea (higher
RT basidiomycetes) component, inhibits differentiation and activation of human
RT macrophages.";
RL Int. J. Med. Mushrooms 17:161-168(2015).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=26952552; DOI=10.1016/j.jep.2016.02.044;
RA Li Z., Wang Y., Jiang B., Li W., Zheng L., Yang X., Bao Y., Sun L.,
RA Huang Y., Li Y.;
RT "Structure, cytotoxic activity and mechanism of protoilludane sesquiterpene
RT aryl esters from the mycelium of Armillaria mellea.";
RL J. Ethnopharmacol. 184:119-127(2016).
RN [7]
RP BIOTECHNOLOGY.
RX PubMed=27592257; DOI=10.1007/s13277-016-5208-6;
RA Chang W.H., Huang H.L., Huang W.P., Chen C.C., Chen Y.J.;
RT "Armillaridin induces autophagy-associated cell death in human chronic
RT myelogenous leukemia K562 cells.";
RL Tumor Biol. 37:14291-14300(2016).
RN [8]
RP MISCELLANEOUS.
RX PubMed=29614282; DOI=10.1016/j.cub.2018.01.026;
RA Sipos G., Anderson J.B., Nagy L.G.;
RT "Armillaria.";
RL Curr. Biol. 28:R297-R298(2018).
RN [9]
RP MISCELLANEOUS.
RX PubMed=30963893; DOI=10.1098/rspb.2018.2233;
RA Anderson J.B., Bruhn J.N., Kasimer D., Wang H., Rodrigue N., Smith M.L.;
RT "Clonal evolution and genome stability in a 2500-year-old fungal
RT individual.";
RL Proc. R. Soc. B 285:20182233-20182233(2018).
RN [10]
RP BIOTECHNOLOGY.
RX PubMed=31488037; DOI=10.1142/s0192415x19500708;
RA Leu Y.S., Chen Y.J., Chen C.C., Huang H.L.;
RT "Induction of autophagic death of human hepatocellular carcinoma cells by
RT armillaridin from Armillaria mellea.";
RL Am. J. Chin. Med. 47:1365-1380(2019).
RN [11]
RP MISCELLANEOUS.
RX PubMed=31746694; DOI=10.1094/pdis-06-19-1147-re;
RA Cromey M.G., Drakulic J., Beal E.J., Waghorn I.A.G., Perry J.N.,
RA Clover G.R.G.;
RT "Susceptibility of garden trees and shrubs to Armillaria root rot.";
RL Plant Dis. 104:483-492(2020).
CC -!- FUNCTION: Cytochrome P450 monooxygenase, part of the gene cluster that
CC mediates the biosynthesis of melleolides, a range of antifungal and
CC phytotoxic polyketide derivatives composed of an orsellinic acid (OA)
CC moiety esterified to various sesquiterpene alcohols (Probable). The
CC first step in melleolides biosynthesis is performed by the delta(6)-
CC protoilludene synthase PRO1 which catalyzes the cyclization of farnesyl
CC diphosphate to protoilludene (PubMed:21148562). The orsellinic acid
CC synthase armB produces OA by condensing acetyl-CoA with 3 malonyl-CoA
CC units in a three-round chain elongation reaction folowed by a C2-C7
CC ring closure (By similarity). ArmB further catalyzes the trans-
CC esterification of OA to the various sesquiterpene alcohols resulting
CC from the hydroxylation of protoilludene (By similarity). The
CC melleolides cluster also includes 5 cytochrome P450 monooxygenases, 4
CC NAD(+)-dependent oxidoreductases, one flavin-dependent oxidoreductase,
CC and one O-methyltransferase (By similarity). The cytochrome P450
CC monooxygenases may be involved in protoilludene hydroxylation to
CC elaborate melleolides with multiple alcohol groups, such as melleolide
CC D, which carries alcohol functionalities at C-4, C-5, C-10, and C-13
CC (By similarity). The role of the NAD(+)-dependent enzymes remains
CC unknown (By similarity). Numerous melleolides, including arnamial, show
CC 5'-O-methylation of the aromatic moiety which may be catalyzed by the
CC methyltransferase encoded in the cluster (By similarity). The flavin-
CC dependent oxidoreductase might represent the dehydrogenase yielding the
CC aldehyde in position 1 of arnamial and other melleolides (By
CC similarity). Finally, several halogenase localized outside of the
CC cluster, are able to catalyze the transfer of a single chlorine atom to
CC the melleolide backbone, resulting in a 6'-chloromelleolide product (By
CC similarity). {ECO:0000250|UniProtKB:I3ZNU9,
CC ECO:0000269|PubMed:21148562, ECO:0000305}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- BIOTECHNOLOGY: Melleolide sesquiterpene aryl esters are cytotoxic
CC secondary products with anti-cancer potential (PubMed:21376582,
CC PubMed:26952552). Armillaridin shows therapeutic and radiosensitizing
CC effects on human esophageal cancer cells (PubMed:23864890).
CC Armillaridin induces autophagy-associated cell death in human chronic
CC myelogenous leukemia as well as of hepatocellular carcinoma cells
CC (PubMed:27592257, PubMed:31488037). Armillaridin can also inhibit the
CC differentiation and activation of human macrophages and thus might have
CC potential to be developed as a biological response modifier for
CC inflammatory diseases (PubMed:25746621). {ECO:0000269|PubMed:21376582,
CC ECO:0000269|PubMed:23864890, ECO:0000269|PubMed:25746621,
CC ECO:0000269|PubMed:26952552, ECO:0000269|PubMed:27592257,
CC ECO:0000269|PubMed:31488037}.
CC -!- MISCELLANEOUS: Armillaria species are both devastating forest pathogens
CC and some of the largest and oldest terrestrial organisms on Earth
CC (PubMed:31746694) (Probable). They forage for hosts and achieve immense
CC colony sizes via rhizomorphs, root-like multicellular structures of
CC clonal dispersal (Probable). One genetic Armillaria gallica individual
CC localized in Michigan's Upper Peninsula stands out as exceptionally
CC large, covering hundreds of tree root systems over approximately 75
CC hectares of the forest floor (PubMed:30963893). Based on observed
CC growth rates of the fungus, the minimum age of this large individual
CC can be estimated as 2500 years (PubMed:30963893).
CC {ECO:0000269|PubMed:30963893, ECO:0000269|PubMed:31746694,
CC ECO:0000305|PubMed:30963893}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KZ293696; PBK84739.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2H3CNS9; -.
DR SMR; A0A2H3CNS9; -.
DR EnsemblFungi; PBK84739; PBK84739; ARMGADRAFT_1018417.
DR OMA; ALHWIVL; -.
DR OrthoDB; 702827at2759; -.
DR Proteomes; UP000217790; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..518
FT /note="Cytochrome P450 monooxygenase ARMGADRAFT_1018417"
FT /id="PRO_0000449411"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 433
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 455
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 518 AA; 57898 MW; 0CDE8A7F84553A49 CRC64;
MALFSAYALA FSLLMIPLIL YILRIGRRES GLPPGPSTLP LVGNLHQLPH GGLHLQFTAW
AKEFGGIFSL KFGPGTVIVA TSPRAVRELI DQKSASTSDR PPSHFSNVIT GGNNIGFARY
SDYWRRGRRV MHSMLTKKAC VNHLTIQRAE ASQLMYDYLV EPKEFVAHGQ RYANSVITSI
LAGTRSPHHT SPLVTAFFQM QHEWTHLLTP GAHPPVDMVP FLKYIPGSWK QICAKMKVSQ
EELYGGMIDA CAKRVERGIR NGCFLEGELE NKDVDRGLLR GMCSALMEGG SDSTSIYLQS
FILMLVAHPE VQAKARAEID SVVGLDRLPD IEDMDNLPYV SAVIKEVLRL RPITALGAPH
YSTQPEVVDG YVIPKNSMIF MNQWGMLHDP DSYDQPESFM PERFLTSPFG TKPGADDTGR
SKDIYFGGGR RICVGMHFGQ NSLAITSMYL IWAFNLTNAI DPQTKNPIPV DINEYDISLN
TIPKPFKCDF QVRSEEHKRM VENAFAEARQ VFAPFEQD
