ARMH4_ARMME
ID ARMH4_ARMME Reviewed; 533 AA.
AC A0A0U3AL34;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Flavin-dependent halogenase armH4 {ECO:0000303|PubMed:26655762};
DE EC=1.14.19.- {ECO:0000269|PubMed:26655762};
DE AltName: Full=ArmH4 {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 [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=DSM 3731;
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 [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 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 [5]
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 [6]
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 [7]
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 [8]
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 [9]
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. Can also
CC catalyze the transfer of a single bromine atom to the melleolide
CC backbone in vitro. {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 -!- CATALYTIC ACTIVITY:
CC Reaction=bromide + FADH2 + melleolide F + O2 = 6'-bromomelleolide F +
CC FAD + 2 H2O; Xref=Rhea:RHEA:67164, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15858, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:58307, ChEBI:CHEBI:167712, ChEBI:CHEBI:167714;
CC Evidence={ECO:0000269|PubMed:26655762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67165;
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; KT819180; ALT31851.1; -; mRNA.
DR AlphaFoldDB; A0A0U3AL34; -.
DR SMR; A0A0U3AL34; -.
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..533
FT /note="Flavin-dependent halogenase armH4"
FT /id="PRO_0000442633"
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 337..338
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P95480"
SQ SEQUENCE 533 AA; 58086 MW; 9781FECB32BC497E CRC64;
MSSLLPPHAQ ILVVGGGPAG SYCASILARE GFSVVVLEAT TFPRYHIGES MLPSVRPFLK
FSGADNKIAS HGFCPKPGAA VKFQQHKREG YTDFSTLSSG NSPDNAAAWN VKRSEFDEIL
LRHAEELGAQ VFENHRVINL IFADNNVSEG RPISAEFSCP NGELRSISFD YLVDASGRAG
IMSTKYLKNR KFNNTLRNVA SWGYWTGAKR YMPGSERDNA PFFEALTDGS GWAWFIPLHD
STVSVGIVTD QASSTARKAL SARNGMHCSS KADYLAQLKL APTVSGKFLC KATLQGENSP
TCIRSASDFS YAADRYSGDH FRLIGDASAF IDPFFSSGVH LALLGALTAA ASISASIRKT
CSELRAAQFH DKKVAIAYTR FLLVVMGVYK QIRNQDLHIL AEVDEDNFDR AFDILRPVIQ
GTADVGKTVS EDELQKTMDF CKDIFAPTDP QMHEAVGARL GPELCSPSVP IMTDSEIEDL
TKDDNEAKLV LKEINARKAV HTMYGGPIHV AAESIDGLVL NLEVGNFGLK NVH
