BET1_NEOBT
ID BET1_NEOBT Reviewed; 2904 AA.
AC A0A0C6E0I7;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2015, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Highly reducing polyketide synthase bet1 {ECO:0000303|PubMed:25530455};
DE Short=HS-PKS bet1 {ECO:0000303|PubMed:25530455};
DE EC=2.3.1.- {ECO:0000269|PubMed:25530455};
DE AltName: Full=Betaenone biosynthesis cluster protein 1 {ECO:0000303|PubMed:25530455};
GN Name=bet1 {ECO:0000303|PubMed:25530455};
OS Neocamarosporium betae (Beet black rot fungus) (Pleospora betae).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Pleosporaceae;
OC Neocamarosporium.
OX NCBI_TaxID=1979465;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP MUTAGENESIS OF SER-2705; TYR-2737 AND LYS-2741, AND PATHWAY.
RX PubMed=25530455; DOI=10.1039/c4cc09512j;
RA Ugai T., Minami A., Fujii R., Tanaka M., Oguri H., Gomi K., Oikawa H.;
RT "Heterologous expression of highly reducing polyketide synthase involved in
RT betaenone biosynthesis.";
RL Chem. Commun. (Camb.) 51:1878-1881(2015).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of betaenones, phytotoxic polyketides
CC involved in leaf spot disease in sugar beets (PubMed:25530455). The
CC first step of the pathway is the synthesis of dehydroprobetaenone I by
CC the polyketide synthase bet1 and the enoyl reductase bet3 via
CC condensation of one acetyl-CoA starter unit with 7 malonyl-CoA units
CC and 5 methylations (PubMed:25530455). The C-terminal reductase (R)
CC domain of bet1 catalyzes the reductive release of the polyketide chain
CC (PubMed:25530455). Because bet1 lacks a designated enoylreductase (ER)
CC domain, the required activity is provided the enoyl reductase bet3
CC (PubMed:25530455). The short-chain dehydrogenase/reductase bet4 then
CC catalyzes reduction of dehydroprobetaenone I to probetaenone I
CC (PubMed:25530455). The cytochrome P450 monooxygenase bet2 catalyzes
CC successive epoxidation, oxidation (resulting from epoxide opening) and
CC hydroxylation to install a tertiary alcohol in the decaline ring to
CC yield betaenone C from dehydroprobetaenone I and betaenone B from
CC probetaenone I (PubMed:25530455). The FAD-linked oxidoreductase (orf1)
CC is probably responsible for the conversion of betaenone C to betaenone
CC A via an intramolecular aldol reaction between C-1 and C-17 to form the
CC bridged tricyclic system in betaenone A (By similarity).
CC {ECO:0000250|UniProtKB:Q0UK53, ECO:0000269|PubMed:25530455}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 10 AH2 + 2 H(+) + 7 malonyl-CoA + 5 S-adenosyl-L-
CC methionine = 10 A + 7 CO2 + 8 CoA + dehydroprobetaenone I + 6 H2O + 5
CC S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:51348, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:145061; Evidence={ECO:0000269|PubMed:25530455};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51349;
CC Evidence={ECO:0000269|PubMed:25530455};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8A5};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:Q9Y8A5};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:25530455}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; an
CC acyl-carrier protein (ACP) that serves as the tether of the growing and
CC completed polyketide via its phosphopantetheinyl arm; and a C-terminal
CC reductase (R) domain that catalyzes the reductive release of the
CC polyketide chain. {ECO:0000269|PubMed:25530455}.
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DR EMBL; LC011911; BAQ25466.1; -; Genomic_DNA.
DR SMR; A0A0C6E0I7; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013120; Far_NAD-bd.
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; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2904
FT /note="Highly reducing polyketide synthase bet1"
FT /id="PRO_0000448649"
FT DOMAIN 2407..2486
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 9..444
FT /note="Ketoacyl synthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 553..875
FT /note="Acyl transferase (AT) domain"
FT /evidence="ECO:0000255"
FT REGION 971..1255
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1411..1596
FT /note="Methyltransferase (cMeT) domain"
FT /evidence="ECO:0000255"
FT REGION 2125..2298
FT /note="Ketoreductase (KR)domain"
FT /evidence="ECO:0000255"
FT REGION 2492..2543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2585..2817
FT /note="Reductase (R) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 2498..2543
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 181
FT /note="For ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2445
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 2705
FT /note="S->A: Blocks the production of dehydroprobetaenone
FT I; when associated with F-2737 and A-2741."
FT /evidence="ECO:0000269|PubMed:25530455"
FT MUTAGEN 2737
FT /note="Y->F: Blocks the production of dehydroprobetaenone
FT I; when associated with A-2705 and A-2741."
FT /evidence="ECO:0000269|PubMed:25530455"
FT MUTAGEN 2741
FT /note="K->A: Blocks the production of dehydroprobetaenone
FT I; when associated with A-2705 and F-2737."
FT /evidence="ECO:0000269|PubMed:25530455"
SQ SEQUENCE 2904 AA; 317655 MW; 42C499A74BC5D248 CRC64;
MSSSASFNEP IAIVGSGCRF AGGASSPSKL WDLLCKPKDI RSDITGRRFN AEGFYHPDGS
HHGHMNVLQS YLLEEDTRLF DAEFFGTNPV EAKAMDPQQR LLLEVVYESI ESAGLCIERL
RGSNTAVFAG LMCGDYEAMM LRDLDQAPTH FATGTSRAVM SNRVSYFFDW RGPSVTIDTA
CSSSLVAVHY AIQALRSGDS HTAVACGSNL IFGPEMYVIE SKLKMLSPDG LGRMWDKDAN
GYARGEGVTA IILKTLSQAL ADNDRIEAVI RETGVNSDGT TPGITMPSAS AQRDLIQSVY
RKAGLDPEAM EDRPQYIEAH GTGTPAGDPI EAEALSTAFF GNTEKASTPI YTGSIKTVLG
HTEGSAGIAA LMKVTQAIRN AILPPNLWFQ QLNPKLKQFY GNLQIPTQAL PWPTVSDRRP
KRASINNFGF GGTNAHAIVE SYEPEPRQTV ESPDAATVST PFVFSAASTE SLRSNLAAYA
TYLDANPKTS AGDLAYTLRE RRSVLPFRIA FPDTTVESLK LSITTRLVEP GNESLGVRTW
TAGNRGRSRL LGVFTGQGAQ YARMGAELVN QAVLAGQLLE KLEGYLSELP EGDRPSWSLR
DEMLADGPLS HVGEAAISQP LCTAVQIILV DLLKSAKVKF DTVVGHSSGE IGAAYAAGYL
SARDALLIAY FRGLHCKHAT SPNGDIKGAM LAAGTSMEDA IEICEAEEFL GRVTVAASNS
SSSVTFSGDE DAIDEIAAVL QDENKFNRRL KVDTAYHSSH MLPCFDLYVA SLRRAGVKAL
LGNGECTWIS SVYEGRSIDP STDELSGVYW AHNMTKAVLF SQAVRAAVKI ATDNDPYTAV
LEVGPHAALA GPAKQNIFEA LQKELPYHGT LLRGGNAMTA FSTCLGFLWT HLDTASIDLG
SCEAAHSGNK QQFTVLGDLP SYQWKHESAY WAESRKSRQM RLRNQPFHQL LGDVSPDSAP
HILRWKNILK PREMTWLEGH QVQSQVVLPA ASYVSTAIEA AQSLASGKKI QLIELSNFHI
HNAITFDQND IGIEVHIEVS NIYIKENQVH ANFTYSAALG DELNDLVLAA NGELKVVLVD
ETPNISLFPQ RQAPPPHMIP VQPSRLYGFM KGLEYDFSGA FQSLIKLERN LGHATCLAQK
AKVLVPDADE LLVHPIDLDA AFQSVMLAYS YPGDDQLRLL HLPTSIAKLR VNPSVLASQR
YAENDMTLID STCSTGDRAE PGDGFSGSVN MYAPGFDHAA IQVDRVKFKP VGSDASNDRD
VFYKMHWVPS AADGMLAAAS VLVGEQDREL MFVLSRIAAY YLRIFDEQLP ENDPARSTSP
LCHYMNYARH MTNLLKNGQH QWAHQDWLND TEEDVLDDIV AKGFMENSDV KIMLLVGNTM
PRVFKGETTM LEHFRTSGLL DEYYSNGFGT KQSTLWVASI LKQLTDRNPH LNMLEIGAGT
GGATKTILQS IGHDFGSYTF TDISSSFFEN AAETFSDWQD SMVFKVCNAE IDPVQQGFQH
GSYDVVIAFM VVHACARLDE AVANLRKLLK PGGLLVLGEG ASDGAMQAGA GFIFGTLPGW
WRGADEGRTL SPLVNASEWD VILKGSGFSG IDTMSPPTLF NAFGITLFVS TAIDERIEFA
RNPLAITKST VYNKVVIVGG RTPPIVQLSR EIQEALIPLA KQVLSYASLE DLDENTLEDE
TVVVSLVDLE APVFKGITSE RWYKFRKLFE TKRDILWLTS GRLEDEPYCN MTVGFGRSAM
HEEETLRIQY VDVTNVGNFD AQKIAQYLLR FTSARLDDKD ILYTKEPEII IDDEGRELVP
RLFTIKASND RLNSTTRSIF DPVDINKHVV ELQYGKDGPN FRQLSRYELS EEPTTPQSDH
AELRLTSSTV SAIRCPTGYQ FLVVGTDQTG AQRLALTSSL TSLLRIPLES TVLCEHPGLS
EANYLGLVAA ELSVIAFCDS LFTGQKLAVH NAPASIVRAV LSHVSPKGLS VTFTTDTLGT
AVSPDVASQI HIPMFSARSD IEAILPSDIV CFVDFSASIQ AENVAMITSC LPSYCRKENV
NTIFSPHGID TSASTAVLGQ LLNRAVNIVK ERNVSTTPTL LGLKALAHGE SGTDPLTIIE
WTGCTTVPAR VTRFESNQLF KSHKTYWLVG LSGALGISLC DWMIERGVRY LVLTSRNPKI
DPRWIRNHER NGVTIKIMLC DVTDEKAINE VHAEIVKTLP PIVGLLNGAM VLRDVSVRNM
EFDQVTDVIR PKVLGSIHLD RIFYNIDLDF FVLLSSINCV IGNVGQANYA AANMGMIGVA
GNRRKRGLRS SVVNVGAIIG VGYITQSDRQ LDVTVAKTAM MHLSEQDFHQ IFAECMEASH
LDSPNGPEIS TGLLSITPET IDIPPWYSDP KFARFRVHKA ADTGDKSDAT NSASTQDLLQ
ACRSQIEVAN VIKQAYCTQL RKMLQVSTVD GDLMMMRGVD LGFDSLLSVD VRSWFLKNFR
VSIPVLKIMA NDVRMSSLVE LAAESIPAEL VPGVPQANAN PNGPSSPDSD ATESSNQNSD
VDVTSTRATS PSTPAATSPD SNVKIKTNSS FAVDWKFETI PPEPFALPGL SDAPKPRENP
EVVVLTGCSG LLGHHLLNTL IAQPSICKII CLAVRRLSSR LESGDLPAPS ERICYYEGDL
TSTYFGLDTT TWTSIFHETD AVIHNGSDTS HLKYYSALKQ ANVESTKQLV STCLQRMIPL
HYISSAGVAL FAGLAAFPPI SCTQTGKTPP ADGSHGYMCG KWVCEKMLER THEKHRLRIV
IQRPSTIIRD GKDATVERAG FDWVNSLLHF AHKTQTVPRV EFNAGAFDLV SVETCCEDVV
RELPNRGREG ITYVNNVGDV VIPMAQMADV GLSKVEKRYS VLPMEEWTKI VVNAGMHPAV
AALIETFDEP GVEKYPALLR SEDA
