ARMB_ARMME
ID ARMB_ARMME Reviewed; 2209 AA.
AC I3ZNU9;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2012, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Orsellinic acid synthase armB {ECO:0000303|PubMed:23993460};
DE Short=OAS {ECO:0000303|PubMed:23993460};
DE EC=2.3.1.- {ECO:0000269|PubMed:23993460};
DE AltName: Full=Melledonol synthase {ECO:0000303|PubMed:23993460};
DE AltName: Full=Melleolides biosynthesis cluster protein armB {ECO:0000303|PubMed:23993460};
DE AltName: Full=Non-reducing polyketide synthase armB {ECO:0000303|PubMed:23993460};
GN Name=armB {ECO:0000303|PubMed:23993460};
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=23078836; DOI=10.1016/j.fgb.2012.09.009;
RA Lackner G., Misiek M., Braesel J., Hoffmeister D.;
RT "Genome mining reveals the evolutionary origin and biosynthetic potential
RT of basidiomycete polyketide synthases.";
RL Fungal Genet. Biol. 49:996-1003(2012).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=23993460; DOI=10.1016/j.chembiol.2013.07.009;
RA Lackner G., Bohnert M., Wick J., Hoffmeister D.;
RT "Assembly of melleolide antibiotics involves a polyketide synthase with
RT cross-coupling activity.";
RL Chem. Biol. 20:1101-1106(2013).
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 FUNCTION.
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 [6]
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 [7]
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 [8]
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 [9]
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 [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: 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
CC (PubMed:23993460). The first step in melleolides biosynthesis is
CC performed by the delta(6)-protoilludene synthase PRO1 which catalyzes
CC the cyclization of farnesyl diphosphate to protoilludene (By
CC similarity). The orsellinic acid synthase armB produces OA by
CC condensing acetyl-CoA with 3 malonyl-CoA units in a three-round chain
CC elongation reaction folowed by a C2-C7 ring closure (PubMed:23993460).
CC ArmB further catalyzes the trans-esterification of OA to the various
CC sesquiterpene alcohols resulting from the hydroxylation of
CC protoilludene (PubMed:26655762). The melleolides cluster also includes
CC 5 cytochrome P450 monooxygenases, 4 NAD(+)-dependent oxidoreductases,
CC one flavin-dependent oxidoreductase, and one O-methyltransferase
CC (Probable). 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 (Probable). The role of the
CC NAD(+)-dependent enzymes remains unknown (Probable). Numerous
CC melleolides, including arnamial, show 5'-O-methylation of the aromatic
CC moiety which may be catalyzed by the methyltransferase encoded in the
CC cluster (Probable). The flavin-dependent oxidoreductase might represent
CC the dehydrogenase yielding the aldehyde in position 1 of arnamial and
CC other melleolides (Probable). Finally, several halogenase localized
CC outside of the cluster (armH1 to armH5), are able to catalyze the
CC transfer of a single chlorine atom to the melleolide backbone,
CC resulting in a 6'-chloromelleolide product (PubMed:26655762).
CC {ECO:0000250|UniProtKB:P0DL13, ECO:0000269|PubMed:23993460,
CC ECO:0000269|PubMed:26655762, ECO:0000305|PubMed:26655762}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 2 H(+) + 3 malonyl-CoA = 3 CO2 + 4 CoA +
CC orsellinate; Xref=Rhea:RHEA:62972, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16162, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384;
CC Evidence={ECO:0000269|PubMed:23993460};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62973;
CC Evidence={ECO:0000269|PubMed:23993460};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:23993460}.
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:0000305|PubMed:23993460}.
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:0000269|PubMed:23993460}.
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}.
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DR EMBL; JQ801748; AFL91703.1; -; Genomic_DNA.
DR AlphaFoldDB; I3ZNU9; -.
DR SMR; I3ZNU9; -.
DR BioCyc; MetaCyc:MON-20281; -.
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; Transferase; Virulence.
FT CHAIN 1..2209
FT /note="Orsellinic acid synthase armB"
FT /id="PRO_0000442629"
FT DOMAIN 1659..1734
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 914..1239
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1335..1610
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
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 1930..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 1008
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000250|UniProtKB:J4UHQ6"
FT MOD_RES 1693
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; 237667 MW; 1A15926E82179125 CRC64;
MSPSLVVPVF AGHGTTAINS TSLRERAVTD ASSSSGALLL DACYYAFNVE LSTLSPSEAS
AVGINPDHFK DPKSLLLLPS HEHYFTNSVV TAATLFLVQT LRYLASVQAS SSASFASTLQ
MNSEHGLGIV GFSSGILPAC VVGSSETTLE FISNAVETFR LAFWIGVRLQ VHKASVETPE
LLGESPLPWS LAFLSMSPAA AESAIQSFHK SFEGTPELRV TSVVSETSVT ISGRPDILAA
FAAQLPPSGP VHKTTVDALY HSSSHHDGVR SQVLADVIRR NIRFPTHADI KIPVRSTYSG
ELLNKSPEGS ASFVEQVIDM ILTQPVNWDK VTEALVRAAP EAEVVHLLNF GPGAGLTKGI
ERYFPSGKVS SIDLSTEAVH TSTLQMPSSV QEPIAICGMS VNMPGAQSVA KLWEVLEKGI
NTVSEVPEHR FKVSDYNDPK KKSRTMAAHT GNFIDEPDAF DNKFFNISPR EARSMDPQQR
VLLHTAYEAL EDAGYVPNST PTNNPETFGC YVGVATNDYV QNLRNDIDVY YSTGTLRAFL
SGRISYALQF SGPSIVVDTA CSSSLIAVYQ ACRALMNRDC NAAVAGGVNV IGSPDMFLGL
DRGHFLSPTG QCKAFDASAD GYSRSEGCGI FVLKRLSDAV AENDQILGVI RGVEVNQSGN
AYSITRPHAP TQENLFTQTL ERSGLDASRI SVVEAHGTGT QAGDPIELES IRGIFAKNRK
TNNPLHITSV KANIGHLEAA SGAAALAKLL LMLRHRTIPR LISLKNLNPR IKPLASDNVI
IDTKQVAWAV PDESLPRVAL LNNFGAAGSN GALLLEEYIP KSSEKIEVSS TFIVGLSAKN
EQALVDLRAS YIEYLRSPAS AGVSLADIAY TATARRRIFS HRFAVTVKSK EELAHKLELA
SGKTVSDKAP GKVVFVFSGQ GGQYLGMGSA LYKTSTLFKS AIDECEYFLK KNNFPGVLPI
ITSDGESSEL TPVEEFEANQ AAIFALEYGL AKLWMSWGVT PTAVVGHSLG EYAAHVVAGV
LSLESALTLV AHRVRIMMRT CELDTTGMIA INLGSGAVTD ILSSSPDFSG ISIACYNSAT
DCVASGAIGQ LDALKAHLDK NVHCKSVRLK VPFGYHSSAM QPLLEEFGAL AKRVTVHAPK
IPVISNPLGR VVREGDKSAF NAEYYLSHCA DPVQFESGIS ALIDDVSFMD IAAWIELGPH
PTTLPMLTVH PGVSKEALLV GSLKKRQDDN LTLSSSLSQL YTSNVPVQWR DVFADVSAAC
VSLPSYPWQK SKFWVAWKED SPAPASSTEG SPAPTKAFNP VNDFGMLQSW AQFPSAANSQ
TAIFETPISL LKTSITGHIV GDVPLCPASV YHELALAGIE ASKAHLSLPL QGSHSALFNI
DYVKPLVYSK DVARVVKTTI AMNTDGSGTF TVESYADSEP ESVHCSGQFR PLLVADTTTK
FNRMAPVVSR RTAAICSGED DEAEVITTRT AYEIIFTRVV RYAKEYHTMK NVTISKNGME
GYAIVKLPKD HDRSKFVVHP VFMDTMLHVA GFLANMQGGD NDAYICSKVK SVKAVPSLIN
NDATYGVFVV NAWVESEGIM LSDAIAVDIS EHGQIVAQLK GMCFKKLRLN TLQRSLAMHA
GHTSPAPAPK RTVAAAPKPK ITEVAPALGP RSSPAKRSVD VQNTVLKIIG DTCGIEVSAL
DVNADLETYG VDSLMSIEIL RKFEESFLQM QFDTTIFSTC NNITELVREI SSTIGSQAAT
AVNTPETAST PEPTLQGDAP QSTDVRSILL ELISSFTGFE ISSFDLNADA DSAYGLDKFL
FIPLFSKLQS FFPDVTLDPA KPSVCSTIGE LLDEVTAQVQ AGPSSSSPGI VDTKPMFVSV
LGLDESDIQD DTEFETIGLD SLTAIEALHA IQTKYGLELP SNLFELHNTV KAVNQYISSK
QPGKSPKPSE EATMDPDKEE DLSDLTPEQV QSVVRVLRLD EVPMSVQKSS SSGSPLFLFH
DGSGAVNYLR RLGSVGREFW GFNNPNYATG KPWGSVEAMA SAYADYAVKV AGSRPVIFGG
WSFGGVVGFE AARQLMRRGV PVKGVVLIDS PFPVDHVPSS NEFMAVTAGA FTRGGRTPIG
RMMWKQLQQN APLLKTYDPR IAGGPYPPLV LLHNQEGIPP DAFLPYPVPR WMSEKGTDPC
LLADDWSGLV GASIKVIHLP GTHFTTFATP HLGAVTQALV DGCAYLDEL
