ARMOM_ARMGA
ID ARMOM_ARMGA Reviewed; 473 AA.
AC A0A2H3CSB7;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2018, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=O-methyltransferase ARMGADRAFT_1088206;
DE EC=2.1.1.-;
DE AltName: Full=Melleolide biosynthesis cluster protein ARMGADRAFT_1088206;
GN ORFNames=ARMGADRAFT_1088206;
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: O-methyltransferase, part of the gene cluster that mediates
CC the biosynthesis of melleolides, a range of antifungal and phytotoxic
CC polyketide derivatives composed of an orsellinic acid (OA) moiety
CC esterified to various sesquiterpene alcohols (Probable). The first step
CC in melleolides biosynthesis is performed by the delta(6)-protoilludene
CC synthase PRO1 which catalyzes the cyclization of farnesyl diphosphate
CC to protoilludene (PubMed:21148562). The orsellinic acid synthase armB
CC produces OA by condensing acetyl-CoA with 3 malonyl-CoA units in a
CC three-round chain elongation reaction folowed by a C2-C7 ring closure
CC (By similarity). ArmB further catalyzes the trans-esterification of OA
CC to the various sesquiterpene alcohols resulting from the hydroxylation
CC of protoilludene (By similarity). The melleolides cluster also includes
CC 5 cytochrome P450 monooxygenases, 4 NAD(+)-dependent oxidoreductases,
CC one flavin-dependent oxidoreductase, and one O-methyltransferase (By
CC similarity). The cytochrome P450 monooxygenases may be involved in
CC protoilludene hydroxylation to elaborate melleolides with multiple
CC alcohol groups, such as melleolide D, which carries alcohol
CC functionalities at C-4, C-5, C-10, and C-13 (By similarity). The role
CC of the NAD(+)-dependent enzymes remains unknown (By similarity).
CC Numerous melleolides, including arnamial, show 5'-O-methylation of the
CC aromatic moiety which may be catalyzed by the methyltransferase encoded
CC in the cluster (By similarity). The flavin-dependent oxidoreductase
CC might represent the dehydrogenase yielding the aldehyde in position 1
CC of arnamial and other melleolides (By similarity). Finally, several
CC halogenase localized outside of the cluster, are able to catalyze the
CC transfer of a single chlorine atom to the melleolide backbone,
CC resulting in a 6'-chloromelleolide product (By similarity).
CC {ECO:0000250|UniProtKB:I3ZNU9, ECO:0000269|PubMed:21148562,
CC ECO:0000305}.
CC -!- PATHWAY: Secondary metabolite biosynthesis. {ECO:0000305}.
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 class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000255|PROSITE-ProRule:PRU01020}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KZ293696; PBK84750.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2H3CSB7; -.
DR SMR; A0A2H3CSB7; -.
DR EnsemblFungi; PBK84750; PBK84750; ARMGADRAFT_1088206.
DR OMA; FEWMERP; -.
DR OrthoDB; 817726at2759; -.
DR Proteomes; UP000217790; Unassembled WGS sequence.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..473
FT /note="O-methyltransferase ARMGADRAFT_1088206"
FT /id="PRO_0000449407"
FT ACT_SITE 352
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 276..277
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 299
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 330..331
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 348
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
SQ SEQUENCE 473 AA; 51579 MW; 4F96515483A03BA8 CRC64;
MPSSLKLLSN LIAESVDKIE QRCAAQGVPF PELNEVLSFQ SEAIRSDTDV AEAIQVIAAS
AAQLLATAMS PIATLSVVAH QWDVPACLGA ANDANVAEIL RDAGPKGAHI DDIAKRNGTN
AGRLGRVLRL LASHHIFREV SPDVFANNRI SSLLDSKKPV EELEKNPQSK YTETSLVNTF
VSFGAGEFFK GGAFLSETLR DPVFGHSDEA NHSAFNKAFK FDVSFFEWME RPENKDVLSR
FSLMMRATTD LLPDAAILNG FDFGSLPDGA LVVDVAGGIG SLSMVLAKTF PKLNFVVEDR
PQLASDAEPY WKSNLPEALE SGRVRLVAHD MFTPQPDLGS PVDVFVLRGI LHDWADSYGI
RLLSHLRAAA GPQTKLVVIE ILLESPCRDP ETSTIKGCEP RTVPEPLLAN MGAADSVDYS
MDMMMMGFGN GQERTLRHYV KILSETGWEL KEVIHIDSLH IGPLRPHLIA VPV
