MOKB_MONPI
ID MOKB_MONPI Reviewed; 2547 AA.
AC Q3S2U6;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Lovastatin diketide synthase mokB {ECO:0000303|PubMed:18578535};
DE EC=2.3.1.244 {ECO:0000269|PubMed:19693441};
DE AltName: Full=Monacolin K biosynthesis protein B {ECO:0000303|PubMed:18578535};
GN Name=mokB {ECO:0000303|PubMed:18578535};
OS Monascus pilosus (Red mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Monascus.
OX NCBI_TaxID=89488 {ECO:0000312|EMBL:ABA02240.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=18578535; DOI=10.1021/jf800595k;
RA Chen Y.P., Tseng C.P., Liaw L.L., Wang C.L., Chen I.C., Wu W.J., Wu M.D.,
RA Yuan G.F.;
RT "Cloning and characterization of monacolin K biosynthetic gene cluster from
RT Monascus pilosus.";
RL J. Agric. Food Chem. 56:5639-5646(2008).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=19693441; DOI=10.1007/s10529-009-0093-3;
RA Sakai K., Kinoshita H., Nihira T.;
RT "Identification of mokB involved in monacolin K biosynthesis in Monascus
RT pilosus.";
RL Biotechnol. Lett. 31:1911-1916(2009).
RN [3]
RP INDUCTION.
RX PubMed=19968298; DOI=10.1021/jf903139x;
RA Chen Y.-P., Yuan G.-F., Hsieh S.-Y., Lin Y.-S., Wang W.-Y., Liaw L.-L.,
RA Tseng C.-P.;
RT "Identification of the mokH gene encoding transcription factor for the
RT upregulation of monacolin K biosynthesis in Monascus pilosus.";
RL J. Agric. Food Chem. 58:287-293(2010).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=21821946; DOI=10.1271/bbb.110195;
RA Hong S.Y., Oh J.H., Lee I.;
RT "Simultaneous enrichment of deglycosylated ginsenosides and monacolin K in
RT red ginseng by fermentation with Monascus pilosus.";
RL Biosci. Biotechnol. Biochem. 75:1490-1495(2011).
CC -!- FUNCTION: Diketide synthase; part of the gene cluster that mediates the
CC biosynthesis of monakolin K, also known as lovastatin, and which acts
CC as a potent competitive inhibitor of HMG-CoA reductase
CC (PubMed:18578535). Monakolin K biosynthesis is performed in two stages
CC (PubMed:19693441). The first stage is catalyzed by the nonaketide
CC synthase mokA, which belongs to type I polyketide synthases and
CC catalyzes the iterative nine-step formation of the polyketide
CC (PubMed:18578535, PubMed:19693441). This PKS stage completed by the
CC action of dehydrogenase mokE, which catalyzes the NADPH-dependent
CC reduction of the unsaturated tetra-, penta- and heptaketide
CC intermediates that arise during the mokA-mediated biosynthesis of the
CC nonaketide chain and leads to dihydromonacolin L (PubMed:19693441).
CC Covalently bound dihydromonacolin L is released from mokA by the mokD
CC esterase (By similarity). Conversion of dihydromonacolin L into
CC monacolin L and then monacolin J is subsequently performed with the
CC participation of molecular oxygen and P450 monoogygenase mokC
CC (PubMed:19693441). Finally, mokF performs the conversion of monacoline
CC J to monacoline K through the addition of the side-chain diketide
CC moiety (2R)-2-methylbutanoate produced by the diketide synthase mokB
CC (PubMed:19693441). {ECO:0000250|UniProtKB:Q0C8M2,
CC ECO:0000250|UniProtKB:Q9Y7D5, ECO:0000269|PubMed:19693441,
CC ECO:0000303|PubMed:18578535}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 H(+) + holo-[2-methylbutanoate polyketide synthase] + 2
CC malonyl-CoA + 2 NADPH + S-adenosyl-L-methionine = (S)-2-
CC methylbutanoyl-[2-methylbutanoate polyketide synthase] + 2 CO2 + 2
CC CoA + H2O + 2 NADP(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:42852, Rhea:RHEA-COMP:10260, Rhea:RHEA-COMP:10261,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:58349, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:82764; EC=2.3.1.244;
CC Evidence={ECO:0000269|PubMed:19693441};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:Q9Y7D5};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:Q9Y7D5};
CC -!- PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis.
CC {ECO:0000269|PubMed:19693441}.
CC -!- INDUCTION: Expression is controlled by the monacolin K cluster
CC transcription regulator mokH (PubMed:19968298).
CC {ECO:0000269|PubMed:19968298}.
CC -!- DISRUPTION PHENOTYPE: Imairs the production of monacolin K and leads to
CC the accumulation of the monacolin J intermediate (PubMed:19693441).
CC {ECO:0000269|PubMed:19693441}.
CC -!- BIOTECHNOLOGY: Monacoline K acts as an inhibitor of HMG-CoA reductase
CC involved in cholesterogenesis (PubMed:21821946). Its
CC hypocholesterolemic activity might be useful for lowering cholesterol
CC levels in the blood and reduce artherosclerosis and coronary heart
CC disease (PubMed:21821946). {ECO:0000269|PubMed:21821946}.
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DR EMBL; DQ176595; ABA02240.1; -; Genomic_DNA.
DR AlphaFoldDB; Q3S2U6; -.
DR SMR; Q3S2U6; -.
DR UniPathway; UPA00875; -.
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:0031177; F:phosphopantetheine binding; IEA:InterPro.
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; 1.10.1200.10; -; 1.
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; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR011032; GroES-like_sf.
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; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
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; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 3.
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; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Disulfide bond; Methyltransferase; Multifunctional enzyme;
KW NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2547
FT /note="Lovastatin diketide synthase mokB"
FT /id="PRO_0000436281"
FT DOMAIN 2459..2541
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 3..432
FT /note="Beta-ketoacyl synthase"
FT /evidence="ECO:0000250|UniProtKB:Q9Y8A5"
FT REGION 545..890
FT /note="Acyl and malonyl transferase"
FT /evidence="ECO:0000250|UniProtKB:Q9Y8A5"
FT REGION 973..985
FT /note="Dehydratase-like"
FT /evidence="ECO:0000250|UniProtKB:Q9Y8A5"
FT REGION 1510..1547
FT /note="Methyltransferase"
FT /evidence="ECO:0000250|UniProtKB:Q9Y8A5"
FT ACT_SITE 183
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 635
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 973
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2501
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DISULFID 1340..1379
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 2547 AA; 278173 MW; 9DA298ACBBBAA000 CRC64;
MKATAASGTP TPIAVVGMGC RFAGGATDPQ ALWKLLEQGG STWSKTPSSR FNVSGVYHPN
GQRVGSMHVR GGHFLDQDPA LFDASFFNMT SEVASCMDPQ QRLILEVVYE ALEAAGIPLE
SVAGSNTAVF SGAMYHDYQD SLHRNPETLP RYFITGNAGT MMSSRVSHFY DLRGPSVTVD
TACSTTLTAL HLAIQSIRAG EADMAIVAGS NLLLNSDVFV TMSNLGFLSP DGISYSFDPR
ANGYGRGEGV AAIILKALPR ALRDGDPIRL VVRETALNQD GRTPAITGPS PEAQACLIRE
CYQKAGLDPR QTSYVEAHGT GTPTGDPLEL AAISAAFQGQ PLQIGSVKAN LGHTEAASGL
ASVMKVALAL EKGIVPPSAR FLQPSKKLLE ERKFQIPLSS QLWLPIDGIC RASINNFGFG
GANAHAIVER YDPAARISTS KPNGHIRPHD SHVEADRGKI YVLSAKDEHS CQEMISRLRD
YLNRANPTDE RQFLANMAYT LASRRSNLRW KAACRAHSLA SLLSVLVSDG TRPRRSAEKA
RLGWVFTGQG AQWFAMGREL IEAYPVFKEA LIECDGYIKG MGANWSIIDE LRRGEAESRV
NEAEFSLPLS TAIQVALVRL LWSWGIRPAA ITSHSSGEVA AAYAVGAFSA RSAIGISYIR
GALIAKTQPA PTTKGGMLAV GLSRSEVGEY ITRVQQQGEE YLVVGCINSP SNVTVSGDLS
AVVRLEELLH ADQIFARRLK VTQAFHSHHM QPLSGEFREA LVEVFNADIT DTTNACQDVV
YASPKTGKRL DDCNHLRDPM HWVESMLFPV EFESSFREMC FDRKDQAQEV DKIIEIGPHG
VLSGAIKQIL QLPELAAFDI SYLSCLSRGK SAVDTIQLLA MDLLQGGYPV DLNAVNFPYG
CEAAEVQVLS DLPTYPWNHK TRYWKEPRIS RAARQRKIPV HDLIGVQEPL CPPLLHLWQN
VLRISDVPWI RDHVVGSRIL FPGAGFISMV IDGLSQICNH DPETCGLSYI LRDVDLAQAL
ILPTDGDEGV DLRLTIRAAD QKSLGMRDWQ RFSVYSIAGD KDDWTEHCTG LIRAQVDHPV
SSSSIQQKTN PPQWSRKMAP QDLWASLHAT GICHGPLFQN IERIESDGQA SWCTLTVADT
VATMPHAYES QHIVHPTTLD SAIQAAYTVL PFMGTLMKTA MVPSRIGGMK IPASFASLEP
GDMLCAQAKI KNQGLSAFTT DVAVFNESDM DEEAGIELEG LTFQSLGAVI SDSRRDLTEN
ESTYSSWHWA PDITLTNSTW LERILSTGTQ SQEIGVMLEL RRCTVHFIQE AIENLTTEDV
ERLSGHLVKF YCWMQAQLAC ATNGELGQDS ADWLRDSEQE RQSLRSRVVA ATNNGEMICR
LGPKLSAILR GELDPLELMM DGQLLSRYYI RAIKWSRSNT QASELVRLCC HKNPRARILE
IGGGTGGCTQ LIVNALGPTK PVGRYDFTDV SAGFFEAARK RFSGWQDVMD FRKLDIEGDP
EVQGFDCGSY DVVLACQVLH ATSNMQRTLN NVRKLLKPGG KLILVETTRD QLDLFFTFGL
LPGWWLSEEP ERQLTPSLSP ELWRSVLSAT GFSGVDLEVR DCDSDEFYMI STMMSTATPG
TPATTLNGPA EVLLVHAGSP PPMDWLQNLQ VALGGKNSSI TSLKALQGVS DLKGKMCVFL
GEMDRTLLES VVSDDFTSLT SMLQYSQGTL WVTRGAAMAS DDPRKALHLG LLRTLRNENH
GRRFVSLDLD PLRDPWTAQS CDAIVNVLNA VGASHEKEFE YAERDGTIHV PRTFSDSSSS
EKEDLVVLEP FQNETRLVRL DVQTPGLLDS LHFKLCSADE AWSSELPEDW VEIEPRAFGL
NFRDIMVAMG QLESNRVMGF ECAGVVTRLS KAATTGAGGL AIGDRVCALM KGHWASRVRT
ARTNVICIPG TLSFEQAASI PLAFTTAYTS LYTVARLQRG EKVLIHGGAG GVGQAAIILA
QLVGAEVFTT AGTHSKRNFL IDKFKLAPDH VFSSRDSGFI EGIRACTNGK GVDVVLNSLA
GPLLQYSFDC LVNFGRFVEI GKKDLEQNSR LNMATFARNV SFSSIDILYW EEAKSAEIFR
ALTEIMRLLE QKTIDLIGPI SEYPMSAIEK AFRTMQSGQH VGKLVVATAE TDMIPVRRGT
MPVALKLDAS YLIVGGLGGI GRRICEWMVD HGARHLLILS RSGRTDPFVT GLQKRGCVVR
IHSCDVADES QLHAVLQQCH EDNMPPIRGI IQAAMVLKDA LVSQMTADDF HVALRPKVQG
SWNLHKIASE VDFFIMLSSL VGVMGGAGQA NYAAAGAFQD ALAQHRVAQG KPAVTIDLGM
VKSIGYVAET DPAVAERLAR IGYQPMHEEE VLAVLERAMS PSSSSAPPSS NPTIPASPAV
IVTGINTGPG PHFTNADWMQ EARFAGIKYR DPLKDDRGGA LSSSQPADED SVRARLSRAS
TEEEATALVV QVMGHRLVTM FGLTESEMSA TQTLSSVGVD SLVAIELRNW ITAQLNVDIS
VFELMEGRTI AEVAEVVVKK YGVGSKV
