PRO1_ARMOS
ID PRO1_ARMOS Reviewed; 342 AA.
AC A0A284RNH4;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2017, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Delta(6)-protoilludene synthase {ECO:0000250|UniProtKB:P0DL13};
DE EC=4.2.3.135 {ECO:0000250|UniProtKB:P0DL13};
DE AltName: Full=Melleolides biosynthesis cluster protein PRO1 {ECO:0000250|UniProtKB:P0DL13};
GN Name=PRO1 {ECO:0000250|UniProtKB:P0DL13}; ORFNames=ARMOST_13672;
OS Armillaria ostoyae (Armillaria root rot fungus).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Physalacriaceae; Armillaria.
OX NCBI_TaxID=47428;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C18/9;
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 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: Delta(6)-protoilludene synthase, part of the gene cluster
CC that mediates the biosynthesis of melleolides, a range of antifungal
CC and phytotoxic polyketide derivatives composed of an orsellinic acid
CC (OA) moiety esterified to various sesquiterpene alcohols (By
CC similarity). The first step in melleolides biosynthesis is performed by
CC the delta(6)-protoilludene synthase PRO1 which catalyzes the
CC cyclization of farnesyl diphosphate to protoilludene (By similarity).
CC The orsellinic acid synthase armB produces OA by condensing acetyl-CoA
CC with 3 malonyl-CoA units in a three-round chain elongation reaction
CC folowed by a C2-C7 ring closure (By similarity). ArmB further catalyzes
CC the trans-esterification of OA to the various sesquiterpene alcohols
CC resulting 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 halogenases, 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:A0A2H3CTK0,
CC ECO:0000250|UniProtKB:I3ZNU9}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate = Delta(6)-protoilludene +
CC diphosphate; Xref=Rhea:RHEA:34695, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:68655, ChEBI:CHEBI:175763; EC=4.2.3.135;
CC Evidence={ECO:0000250|UniProtKB:I3ZNU9};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:I3ZNU9};
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). An A.ostoyae colony, known as the
CC 'humongous fungus' in the Malheur National Forest in the Strawberry
CC Mountains of eastern Oregon, was found to be the largest fungal colony
CC in the world, spanning an area of 9.1 square kilometers (Probable).
CC This organism is estimated to be some 8,000 years old and may weigh as
CC much as 35,000 tons (Probable). {ECO:0000269|PubMed:31746694,
CC ECO:0000305, ECO:0000305|PubMed:29614282}.
CC -!- SIMILARITY: Belongs to the terpene synthase family. {ECO:0000305}.
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DR EMBL; FUEG01000012; SJL10288.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A284RNH4; -.
DR SMR; A0A284RNH4; -.
DR OMA; ESRFMEN; -.
DR OrthoDB; 1143139at2759; -.
DR Proteomes; UP000219338; Unassembled WGS sequence.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR034686; Terpene_cyclase-like_2.
DR SFLD; SFLDG01020; Terpene_Cyclase_Like_2; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW Lyase; Magnesium; Metal-binding; Reference proteome; Virulence.
FT CHAIN 1..342
FT /note="Delta(6)-protoilludene synthase"
FT /id="PRO_0000449400"
FT MOTIF 81..85
FT /note="DDXXD motif"
FT /evidence="ECO:0000250|UniProtKB:P0DL13"
FT BINDING 81
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 81
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 217
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 221
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 225
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
FT BINDING 322..323
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9UR08"
SQ SEQUENCE 342 AA; 39384 MW; EEBC8D252ACD4A60 CRC64;
MSQRIFLPDT LANWQWPRHL NPHYAEVKKA SAAWAQSFRA FQTKAQEAFD RCDFNLLASF
AYPLADEGDG CDLMNLFFVI DEYSDVSTEE EVRAQKDIVM DAIRNTEKPR PAGEWIGGEV
ARQFWDLAKK TASSQAQKRF IDTFDEYLES VVQQAADRNN SHIRGIESYL EVRRCTIGAK
PSFALLEFDM QLPDEVINHP VIKELEKSCI DMLCLGNDVV SYNLEQARDD DGHNIVTIAM
NELRTDVAGA MIWVDEYHKQ LESRFMENFK KVPRWGGPID LQVARYCDGL GNWVRANDQW
SFESERYFGK KGPEIIQRRW ITLMPKMVSE ELGPQIVDGS HL
