ARMH2_ARMME
ID ARMH2_ARMME Reviewed; 516 AA.
AC G3FLZ8;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 23.
DE RecName: Full=Flavin-dependent halogenase armH2 {ECO:0000303|PubMed:26655762};
DE EC=1.14.19.- {ECO:0000269|PubMed:26655762};
GN Name=armH2 {ECO:0000303|PubMed:26655762};
OS Armillaria mellea (Shoestring root rot fungus) (Honey mushroom).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Physalacriaceae; Armillaria.
OX NCBI_TaxID=47429;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=DSM 3731;
RX PubMed=21802058; DOI=10.1016/j.funbio.2011.06.002;
RA Misiek M., Braesel J., Hoffmeister D.;
RT "Characterisation of the ArmA adenylation domain implies a more diverse
RT secondary metabolism in the genus Armillaria.";
RL Fungal Biol. 115:775-781(2011).
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 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 [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=26655762; DOI=10.1128/aem.03168-15;
RA Wick J., Heine D., Lackner G., Misiek M., Tauber J., Jagusch H.,
RA Hertweck C., Hoffmeister D.;
RT "A fivefold parallelized biosynthetic process secures chlorination of
RT Armillaria mellea (honey mushroom) toxins.";
RL Appl. Environ. Microbiol. 82:1196-1204(2015).
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 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 [10]
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: Flavin-dependent halogenase involved in the biosynthesis of
CC melleolides, a range of antifungal and phytotoxic polyketide
CC derivatives composed of an orsellinic acid (OA) moiety esterified to
CC various sesquiterpene alcohols. The halogenase catalyzes the transfer
CC of a single chlorine atom to the melleolide backbone, resulting in a
CC 6'-chloromelleolide product. The enzyme acts on free substrate and does
CC not depend on carrier-protein-dependent acceptor molecules.
CC {ECO:0000269|PubMed:26655762}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride + FADH2 + melleolide F + O2 = 6'-chloromelleolide F +
CC FAD + H(+) + 2 H2O; Xref=Rhea:RHEA:67160, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:167712,
CC ChEBI:CHEBI:167713; Evidence={ECO:0000269|PubMed:26655762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67161;
CC Evidence={ECO:0000269|PubMed:26655762};
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). {ECO:0000269|PubMed:31746694,
CC ECO:0000305|PubMed:29614282}.
CC -!- SIMILARITY: Belongs to the flavin-dependent halogenase family.
CC {ECO:0000305}.
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DR EMBL; JF739170; AEM76786.1; -; Genomic_DNA.
DR AlphaFoldDB; G3FLZ8; -.
DR SMR; G3FLZ8; -.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR006905; Flavin_halogenase.
DR Pfam; PF04820; Trp_halogenase; 2.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT CHAIN 1..516
FT /note="Flavin-dependent halogenase armH2"
FT /id="PRO_0000442631"
FT REGION 440..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 16..19
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 39..50
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 328..329
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P95480"
SQ SEQUENCE 516 AA; 57179 MW; F8ACE9F18F46A762 CRC64;
MVTQVPSSTN ILVIGGGPAG AYAAGVLVRE GFEVTLLEKD FFPRYHIGES MLPSWRQFLR
FIDMEEKMKN YGFLPKPGGA IKLNQDKREG YTDFIANNPE NSAWNVVRSE FDQLLLNHVA
EQGVKVYEGT RVDEIHFSPE EPTRPVSLTW SKDDKTRGDI SFNWLVDASG RNGLMSTKYL
KNRTFNRSLK NVAVWGYWTG TNRYAPGTNR ENAPWFEALT DETGWVWFIP LHDGTTNVGV
VLVEEDSKRK KAEYRAKHEG KSLAEVQYDR YMEDIQLAPG LIGLLGDGKF DGKLQAAGDY
SYHASGYAGP HFRIAGDAGA FIDPFFSSGI HLAFTGGLSA ACTIAASIRG HCTEEEASEF
HSSKIKTAFT RFLFVVLGIY KQLRAQQSQI LYEADEESLD RAILSLRPVI QGAADADADL
TKEELENTLD FCKSVLEDEP QANGNGAAKQ DAVPAPIPVA LSSGAGPEKD AKRREIEAES
LRSLQEMDDC KRNFGTEVIN GFFVKMEQGV LGLVRA
