ARMB_ARMGA
ID ARMB_ARMGA Reviewed; 2209 AA.
AC A0A2H3CTK0;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2018, sequence version 1.
DT 25-MAY-2022, entry version 21.
DE RecName: Full=Orsellinic acid synthase armB {ECO:0000250|UniProtKB:I3ZNU9};
DE Short=OAS {ECO:0000250|UniProtKB:I3ZNU9};
DE EC=2.3.1.- {ECO:0000250|UniProtKB:I3ZNU9};
DE AltName: Full=Melledonol synthase {ECO:0000250|UniProtKB:I3ZNU9};
DE AltName: Full=Melleolides biosynthesis cluster protein armB {ECO:0000250|UniProtKB:I3ZNU9};
DE AltName: Full=Non-reducing polyketide synthase ArmB {ECO:0000250|UniProtKB:I3ZNU9};
GN Name=armB {ECO:0000250|UniProtKB:I3ZNU9}; ORFNames=ARMGADRAFT_1169973;
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 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 [3]
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 [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=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 [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: Non-reducing polyketide 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 (PubMed:21148562).
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 halogenase localized outside of the
CC cluster (armH1 to armH5), are able to catalyze the transfer of a single
CC chlorine atom to the melleolide backbone, resulting in a 6'-
CC chloromelleolide product (By similarity).
CC {ECO:0000250|UniProtKB:I3ZNU9, ECO:0000269|PubMed:21148562}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000250|UniProtKB:I3ZNU9}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm. {ECO:0000250|UniProtKB:I3ZNU9}.
CC -!- DOMAIN: The release of the polyketide chain from the non-reducing
CC polyketide synthase is mediated by the thioesterase (TE) domain
CC localized at the C-ter of the protein, which accepts the sesquiterpene
CC alcohols as substrate to offload the finished ketide from the PKS
CC assembly line. {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). 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}.
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DR EMBL; KZ293696; PBK84764.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2H3CTK0; -.
DR SMR; A0A2H3CTK0; -.
DR STRING; 47427.A0A2H3CTK0; -.
DR EnsemblFungi; PBK84764; PBK84764; ARMGADRAFT_1169973.
DR OMA; PETFGCY; -.
DR OrthoDB; 68112at2759; -.
DR Proteomes; UP000217790; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 3.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR020802; PKS_thioesterase.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SMART; SM00824; PKS_TE; 1.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF52151; SSF52151; 2.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 1: Evidence at protein level;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase;
KW Virulence.
FT CHAIN 1..2209
FT /note="Orsellinic acid synthase armB"
FT /id="PRO_0000449401"
FT DOMAIN 1660..1735
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1844..1921
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 38..261
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 394..820
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 915..1240
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1336..1611
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1739..1761
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1917..1945
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1962..2201
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 1924..1945
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 561
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1009
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000250|UniProtKB:J4UHQ6"
FT MOD_RES 1694
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1881
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2209 AA; 237208 MW; 921A122A6EF6F9B3 CRC64;
MSPSLVVPVF AGHGTTAINS TSLRERAVAD ASSPSGALLL DACHYAFNVE LSTLSSSEAS
AVGINPDHFT DTKSLLLLPS HEPYLTNSVV TAATLFLVQT LRYLASVQAS SSTSFASTLQ
TNSEHGLGIV GFSSGILPAC VVGSSETTLE FISNAVETFR LAFWIGVRLQ VHKASAQMPE
LLGESPLPWS LAFLGMSHAA AESAIQSFLK SFEDTPELRV TSVVSETSVT ISGRPDILAA
FAAQLPPSGP VHKTTVDALY HSSSHHDGVR SQVLADVKRR NIRFPTHADI KIPVRSTYSG
ELISKGSEGS VSFAEQVVDM ILTQPVNWDK VTDALVHAAP EGTVVHLLNF GPGAGLTKGI
ERYFPSDKVS STDLSSEPAH TSTLQMPSSV QEPIAICGMS VNMPGAPSVA KLWEVLEKGI
NTVSEVPEHR FKVSDYNDPK KKGRTMGAHT GNFIDEPDAF DNKFFNISPR EARSMDPQQR
VLLHTAYEAL EDAGYVPNST PTNNPETFGC YVGVATNDYV QNLRNDIDVY YSTGTLRAFL
SGRISYALQF SGPSIVVDTA CSSSLIAVYQ ACRALMNRDC NAAVAGGVNV ISSPDMFLGL
DRGHFLSPTG QCKAFDASAD GYSRSEGCGI FVLKRLSDAV AENDQILGVI RGVEVNQSGN
AYSITRPHAP TQENLFTQTL ERSGLDASRI SVVEAHGTGT QAGDPIELES IRGIFAKHRK
ANNPLHITSV KANIGHLEAA SGAAALAKLL LMLRHRTIPR LISLKNLNPR IKPLASDNVI
IDTKQVAWTV PDESLPRIAL LNNFGAAGSN GALLLEEYIP KSSRKDTDVA STFVVGLSAK
NEQALVDLRA SYIEYLRSPA SAGVTLADIA YTATARRRIF SHRFAVTAKS KEELTHKLEL
ASGKTVSDNA PGKVVFVFSG QGGQYLGMGS ALYKTSALFK SAIDECEYFL KKNGFPGVLP
IITSDGESSG LTPVEEFEAN QAAIFALEYG LAKLWISWGV TPTAVVGHSL GEYAAHVIAG
VLSLESALTL VAHRVCIMMR TCELDTTGMI AINLGSGAVT DILSSSPDFS DISIACYNSV
TDCVASGPIG QLDALKAHLD KAVHCKSVRL KVPFGYHSSA MQPLLEEFGA LAKRITVHAP
KIPVISNPLG RVIREGDKSA FNAEYYLSHC ADPVQFESGI SALIDDASFT DIAAWIELGP
HPTTLPMLTV HPGVSKEALL VSSLKKRQDD GLTLSSSLSQ LYTSNVPVRW RDVFADVSAA
CVSLPSYPWQ KSKFWVAWKE DSPAPASSTE GSTASTKPFN PVNDFGMLQS WAQFPSTANG
QTAIFETPIS LLKTSITGHI VGDVPLCPAS VYHELALAGI ETSKTHLSLP LQGSHSALFN
IDYVKPLVYS KDVARVVKTT IAINVDGSGT FTVESYAASE PESVHCSGQF RPLLVVDTTT
KFNRMAPVVS RRTAAICSGD DGEAEVFTTR TAYEIIFTRV VRYAKEYHTM KNVTISKNGM
EGYAVVKLPK DHDKSKFVVH PVFMDTMLHV AGFLANMQGG DNDAYICSKV KSVKAVPSLI
SNDATYGVFV VNAWVESEGI MLSDAIAVDI SGHGQIVAQL KGMCFKKLRL NTLQRSLAMH
AGHSAPAPAQ KRVVAAAPKP KITEVAPALG PRSSPAKRSV DVQNTVLNIV GDTCGIEISA
LDVNADLETY GVDSLMSIEI LRKFEESFPQ MQFDATIFST CNNITELVRE ISSTVGSQAA
TAVNTPETAS TPEPTLHGDA SQSTDVRSIL LGLISSFTGF EISSFDLNAD ADTAYGLDKF
LFIPLFSKLQ TFFPDVTLDP TKPSVCSTIG ELLDEVTAQV QAGPSSSPDL IDTKPMFVSV
LGLDESDIQD DTEFETIGLD SLTAIEALHA IQTKYGLELP SNLFELHTTA KAVNQYISSK
RPGKSPKPVE ETAMDPEKDE DLSDLTPEQV QSVVRVLRLD EVPMSVQKSS SSGSPLFLFH
DGSGAVNYLR RLGSVDREFW GFNNPNYATG KPWGSVEAMA SAYADYAVKV AGSRPVIFGG
WSFGGVIGFE AARQLMRRGV PVKGVVLIDS PFPVDHVPSS NEFMAVTSGA FTRGGRTPIG
RMMWKQLQQN APLLKTYDPR IAGGPYPPLV LLHNKEGIPP DAFLPYPVPR WMSEKGTDPC
LLADDWSGLV GAPIKVIHLP GTHFTTFATP HLGAVTQALV DGCAYLDEL
