UniProtKB - Q3S2U6 (MOKB_MONPI)
Protein
Lovastatin diketide synthase mokB
Gene
mokB
Organism
Monascus pilosus (Red mold)
Status
Functioni
Diketide synthase; part of the gene cluster that mediates the biosynthesis of monakolin K, also known as lovastatin, and which acts as a potent competitive inhibitor of HMG-CoA reductase (PubMed:18578535). Monakolin K biosynthesis is performed in two stages (PubMed:19693441). The first stage is catalyzed by the nonaketide synthase mokA, which belongs to type I polyketide synthases and catalyzes the iterative nine-step formation of the polyketide (PubMed:18578535, PubMed:19693441). This PKS stage completed by the action of dehydrogenase mokE, which catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the mokA-mediated biosynthesis of the nonaketide chain and leads to dihydromonacolin L (PubMed:19693441). Covalently bound dihydromonacolin L is released from mokA by the mokD esterase (By similarity). Conversion of dihydromonacolin L into monacolin L and then monacolin J is subsequently performed with the participation of molecular oxygen and P450 monoogygenase mokC (PubMed:19693441). Finally, mokF performs the conversion of monacoline J to monacoline K through the addition of the side-chain diketide moiety (2R)-2-methylbutanoate produced by the diketide synthase mokB (PubMed:19693441).1 PublicationBy similarity1 Publication
Catalytic activityi
- 3 H+ + holo-[2-methylbutanoate polyketide synthase] + 2 malonyl-CoA + 2 NADPH + S-adenosyl-L-methionine = (S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase] + 2 CO2 + 2 CoA + H2O + 2 NADP+ + S-adenosyl-L-homocysteine1 PublicationEC:2.3.1.2441 Publication
Cofactori
pantetheine 4'-phosphateBy similarityNote: Binds 1 phosphopantetheine covalently.By similarity
: lovastatin biosynthesis Pathwayi
This protein is involved in the pathway lovastatin biosynthesis, which is part of Polyketide biosynthesis.1 PublicationView all proteins of this organism that are known to be involved in the pathway lovastatin biosynthesis and in Polyketide biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 183 | For beta-ketoacyl synthase activityPROSITE-ProRule annotation | 1 | |
Active sitei | 635 | For malonyltransferase activityPROSITE-ProRule annotation | 1 | |
Active sitei | 973 | For beta-hydroxyacyl dehydratase activityPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- 3-oxoacyl-[acyl-carrier-protein] synthase activity Source: InterPro
- methyltransferase activity Source: UniProtKB-KW
- oxidoreductase activity Source: UniProtKB-KW
- phosphopantetheine binding Source: InterPro
GO - Biological processi
- fatty acid biosynthetic process Source: InterPro
- methylation Source: UniProtKB-KW
Keywordsi
Molecular function | Acyltransferase, Methyltransferase, Multifunctional enzyme, Oxidoreductase, Transferase |
Ligand | NADP, S-adenosyl-L-methionine |
Enzyme and pathway databases
UniPathwayi | UPA00875 |
Names & Taxonomyi
Protein namesi | Recommended name: Lovastatin diketide synthase mokB1 Publication (EC:2.3.1.2441 Publication)Alternative name(s): Monacolin K biosynthesis protein B1 Publication |
Gene namesi | Name:mokB1 Publication |
Organismi | Monascus pilosus (Red mold)Imported |
Taxonomic identifieri | 89488 [NCBI] |
Taxonomic lineagei | Eukaryota › Fungi › Dikarya › Ascomycota › Pezizomycotina › Eurotiomycetes › Eurotiomycetidae › Eurotiales › Aspergillaceae › Monascus |
Pathology & Biotechi
Biotechnological usei
Monacoline K acts as an inhibitor of HMG-CoA reductase involved in cholesterogenesis (PubMed:21821946). Its hypocholesterolemic activity might be useful for lowering cholesterol levels in the blood and reduce artherosclerosis and coronary heart disease (PubMed:21821946).1 Publication
Disruption phenotypei
Imairs the production of monacolin K and leads to the accumulation of the monacolin J intermediate (PubMed:19693441).1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000436281 | 1 – 2547 | Lovastatin diketide synthase mokBAdd BLAST | 2547 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 1340 ↔ 1379 | PROSITE-ProRule annotation | ||
Modified residuei | 2501 | O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation | 1 |
Keywords - PTMi
Disulfide bond, Phosphopantetheine, PhosphoproteinExpressioni
Inductioni
Expression is controlled by the monacolin K cluster transcription regulator mokH (PubMed:19968298).1 Publication
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 2459 – 2541 | CarrierPROSITE-ProRule annotationAdd BLAST | 83 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 3 – 432 | Beta-ketoacyl synthaseBy similarityAdd BLAST | 430 | |
Regioni | 545 – 890 | Acyl and malonyl transferaseBy similarityAdd BLAST | 346 | |
Regioni | 973 – 985 | Dehydratase-likeBy similarityAdd BLAST | 13 | |
Regioni | 1510 – 1547 | MethyltransferaseBy similarityAdd BLAST | 38 |
Family and domain databases
Gene3Di | 1.10.1200.10, 1 hit 3.10.129.110, 1 hit 3.40.366.10, 1 hit 3.40.47.10, 1 hit |
InterProi | View protein in InterPro IPR001227, Ac_transferase_dom_sf IPR036736, ACP-like_sf IPR014043, Acyl_transferase IPR016035, Acyl_Trfase/lysoPLipase IPR011032, GroES-like_sf IPR018201, Ketoacyl_synth_AS IPR014031, Ketoacyl_synth_C IPR014030, Ketoacyl_synth_N IPR016036, Malonyl_transacylase_ACP-bd IPR013217, Methyltransf_12 IPR036291, NAD(P)-bd_dom_sf IPR032821, PKS_assoc IPR020841, PKS_Beta-ketoAc_synthase_dom IPR020807, PKS_dehydratase IPR042104, PKS_dehydratase_sf IPR020843, PKS_ER IPR013968, PKS_KR IPR020806, PKS_PP-bd IPR009081, PP-bd_ACP IPR006162, Ppantetheine_attach_site IPR029063, SAM-dependent_MTases IPR016039, Thiolase-like |
Pfami | View protein in Pfam PF00698, Acyl_transf_1, 1 hit PF16197, KAsynt_C_assoc, 1 hit PF00109, ketoacyl-synt, 1 hit PF02801, Ketoacyl-synt_C, 1 hit PF08659, KR, 1 hit PF08242, Methyltransf_12, 1 hit PF00550, PP-binding, 1 hit PF14765, PS-DH, 1 hit |
SMARTi | View protein in SMART SM00827, PKS_AT, 1 hit SM00826, PKS_DH, 1 hit SM00829, PKS_ER, 1 hit SM00825, PKS_KS, 1 hit SM00823, PKS_PP, 1 hit |
SUPFAMi | SSF47336, SSF47336, 1 hit SSF50129, SSF50129, 1 hit SSF51735, SSF51735, 3 hits SSF52151, SSF52151, 1 hit SSF53335, SSF53335, 1 hit SSF53901, SSF53901, 1 hit SSF55048, SSF55048, 1 hit |
PROSITEi | View protein in PROSITE PS00606, B_KETOACYL_SYNTHASE, 1 hit PS50075, CARRIER, 1 hit PS00012, PHOSPHOPANTETHEINE, 1 hit |
i Sequence
Sequence statusi: Complete.
Q3S2U6-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKATAASGTP TPIAVVGMGC RFAGGATDPQ ALWKLLEQGG STWSKTPSSR
60 70 80 90 100
FNVSGVYHPN GQRVGSMHVR GGHFLDQDPA LFDASFFNMT SEVASCMDPQ
110 120 130 140 150
QRLILEVVYE ALEAAGIPLE SVAGSNTAVF SGAMYHDYQD SLHRNPETLP
160 170 180 190 200
RYFITGNAGT MMSSRVSHFY DLRGPSVTVD TACSTTLTAL HLAIQSIRAG
210 220 230 240 250
EADMAIVAGS NLLLNSDVFV TMSNLGFLSP DGISYSFDPR ANGYGRGEGV
260 270 280 290 300
AAIILKALPR ALRDGDPIRL VVRETALNQD GRTPAITGPS PEAQACLIRE
310 320 330 340 350
CYQKAGLDPR QTSYVEAHGT GTPTGDPLEL AAISAAFQGQ PLQIGSVKAN
360 370 380 390 400
LGHTEAASGL ASVMKVALAL EKGIVPPSAR FLQPSKKLLE ERKFQIPLSS
410 420 430 440 450
QLWLPIDGIC RASINNFGFG GANAHAIVER YDPAARISTS KPNGHIRPHD
460 470 480 490 500
SHVEADRGKI YVLSAKDEHS CQEMISRLRD YLNRANPTDE RQFLANMAYT
510 520 530 540 550
LASRRSNLRW KAACRAHSLA SLLSVLVSDG TRPRRSAEKA RLGWVFTGQG
560 570 580 590 600
AQWFAMGREL IEAYPVFKEA LIECDGYIKG MGANWSIIDE LRRGEAESRV
610 620 630 640 650
NEAEFSLPLS TAIQVALVRL LWSWGIRPAA ITSHSSGEVA AAYAVGAFSA
660 670 680 690 700
RSAIGISYIR GALIAKTQPA PTTKGGMLAV GLSRSEVGEY ITRVQQQGEE
710 720 730 740 750
YLVVGCINSP SNVTVSGDLS AVVRLEELLH ADQIFARRLK VTQAFHSHHM
760 770 780 790 800
QPLSGEFREA LVEVFNADIT DTTNACQDVV YASPKTGKRL DDCNHLRDPM
810 820 830 840 850
HWVESMLFPV EFESSFREMC FDRKDQAQEV DKIIEIGPHG VLSGAIKQIL
860 870 880 890 900
QLPELAAFDI SYLSCLSRGK SAVDTIQLLA MDLLQGGYPV DLNAVNFPYG
910 920 930 940 950
CEAAEVQVLS DLPTYPWNHK TRYWKEPRIS RAARQRKIPV HDLIGVQEPL
960 970 980 990 1000
CPPLLHLWQN VLRISDVPWI RDHVVGSRIL FPGAGFISMV IDGLSQICNH
1010 1020 1030 1040 1050
DPETCGLSYI LRDVDLAQAL ILPTDGDEGV DLRLTIRAAD QKSLGMRDWQ
1060 1070 1080 1090 1100
RFSVYSIAGD KDDWTEHCTG LIRAQVDHPV SSSSIQQKTN PPQWSRKMAP
1110 1120 1130 1140 1150
QDLWASLHAT GICHGPLFQN IERIESDGQA SWCTLTVADT VATMPHAYES
1160 1170 1180 1190 1200
QHIVHPTTLD SAIQAAYTVL PFMGTLMKTA MVPSRIGGMK IPASFASLEP
1210 1220 1230 1240 1250
GDMLCAQAKI KNQGLSAFTT DVAVFNESDM DEEAGIELEG LTFQSLGAVI
1260 1270 1280 1290 1300
SDSRRDLTEN ESTYSSWHWA PDITLTNSTW LERILSTGTQ SQEIGVMLEL
1310 1320 1330 1340 1350
RRCTVHFIQE AIENLTTEDV ERLSGHLVKF YCWMQAQLAC ATNGELGQDS
1360 1370 1380 1390 1400
ADWLRDSEQE RQSLRSRVVA ATNNGEMICR LGPKLSAILR GELDPLELMM
1410 1420 1430 1440 1450
DGQLLSRYYI RAIKWSRSNT QASELVRLCC HKNPRARILE IGGGTGGCTQ
1460 1470 1480 1490 1500
LIVNALGPTK PVGRYDFTDV SAGFFEAARK RFSGWQDVMD FRKLDIEGDP
1510 1520 1530 1540 1550
EVQGFDCGSY DVVLACQVLH ATSNMQRTLN NVRKLLKPGG KLILVETTRD
1560 1570 1580 1590 1600
QLDLFFTFGL LPGWWLSEEP ERQLTPSLSP ELWRSVLSAT GFSGVDLEVR
1610 1620 1630 1640 1650
DCDSDEFYMI STMMSTATPG TPATTLNGPA EVLLVHAGSP PPMDWLQNLQ
1660 1670 1680 1690 1700
VALGGKNSSI TSLKALQGVS DLKGKMCVFL GEMDRTLLES VVSDDFTSLT
1710 1720 1730 1740 1750
SMLQYSQGTL WVTRGAAMAS DDPRKALHLG LLRTLRNENH GRRFVSLDLD
1760 1770 1780 1790 1800
PLRDPWTAQS CDAIVNVLNA VGASHEKEFE YAERDGTIHV PRTFSDSSSS
1810 1820 1830 1840 1850
EKEDLVVLEP FQNETRLVRL DVQTPGLLDS LHFKLCSADE AWSSELPEDW
1860 1870 1880 1890 1900
VEIEPRAFGL NFRDIMVAMG QLESNRVMGF ECAGVVTRLS KAATTGAGGL
1910 1920 1930 1940 1950
AIGDRVCALM KGHWASRVRT ARTNVICIPG TLSFEQAASI PLAFTTAYTS
1960 1970 1980 1990 2000
LYTVARLQRG EKVLIHGGAG GVGQAAIILA QLVGAEVFTT AGTHSKRNFL
2010 2020 2030 2040 2050
IDKFKLAPDH VFSSRDSGFI EGIRACTNGK GVDVVLNSLA GPLLQYSFDC
2060 2070 2080 2090 2100
LVNFGRFVEI GKKDLEQNSR LNMATFARNV SFSSIDILYW EEAKSAEIFR
2110 2120 2130 2140 2150
ALTEIMRLLE QKTIDLIGPI SEYPMSAIEK AFRTMQSGQH VGKLVVATAE
2160 2170 2180 2190 2200
TDMIPVRRGT MPVALKLDAS YLIVGGLGGI GRRICEWMVD HGARHLLILS
2210 2220 2230 2240 2250
RSGRTDPFVT GLQKRGCVVR IHSCDVADES QLHAVLQQCH EDNMPPIRGI
2260 2270 2280 2290 2300
IQAAMVLKDA LVSQMTADDF HVALRPKVQG SWNLHKIASE VDFFIMLSSL
2310 2320 2330 2340 2350
VGVMGGAGQA NYAAAGAFQD ALAQHRVAQG KPAVTIDLGM VKSIGYVAET
2360 2370 2380 2390 2400
DPAVAERLAR IGYQPMHEEE VLAVLERAMS PSSSSAPPSS NPTIPASPAV
2410 2420 2430 2440 2450
IVTGINTGPG PHFTNADWMQ EARFAGIKYR DPLKDDRGGA LSSSQPADED
2460 2470 2480 2490 2500
SVRARLSRAS TEEEATALVV QVMGHRLVTM FGLTESEMSA TQTLSSVGVD
2510 2520 2530 2540
SLVAIELRNW ITAQLNVDIS VFELMEGRTI AEVAEVVVKK YGVGSKV
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | DQ176595 Genomic DNA Translation: ABA02240.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | DQ176595 Genomic DNA Translation: ABA02240.1 |
3D structure databases
SMRi | Q3S2U6 |
ModBasei | Search... |
Enzyme and pathway databases
UniPathwayi | UPA00875 |
Family and domain databases
Gene3Di | 1.10.1200.10, 1 hit 3.10.129.110, 1 hit 3.40.366.10, 1 hit 3.40.47.10, 1 hit |
InterProi | View protein in InterPro IPR001227, Ac_transferase_dom_sf IPR036736, ACP-like_sf IPR014043, Acyl_transferase IPR016035, Acyl_Trfase/lysoPLipase IPR011032, GroES-like_sf IPR018201, Ketoacyl_synth_AS IPR014031, Ketoacyl_synth_C IPR014030, Ketoacyl_synth_N IPR016036, Malonyl_transacylase_ACP-bd IPR013217, Methyltransf_12 IPR036291, NAD(P)-bd_dom_sf IPR032821, PKS_assoc IPR020841, PKS_Beta-ketoAc_synthase_dom IPR020807, PKS_dehydratase IPR042104, PKS_dehydratase_sf IPR020843, PKS_ER IPR013968, PKS_KR IPR020806, PKS_PP-bd IPR009081, PP-bd_ACP IPR006162, Ppantetheine_attach_site IPR029063, SAM-dependent_MTases IPR016039, Thiolase-like |
Pfami | View protein in Pfam PF00698, Acyl_transf_1, 1 hit PF16197, KAsynt_C_assoc, 1 hit PF00109, ketoacyl-synt, 1 hit PF02801, Ketoacyl-synt_C, 1 hit PF08659, KR, 1 hit PF08242, Methyltransf_12, 1 hit PF00550, PP-binding, 1 hit PF14765, PS-DH, 1 hit |
SMARTi | View protein in SMART SM00827, PKS_AT, 1 hit SM00826, PKS_DH, 1 hit SM00829, PKS_ER, 1 hit SM00825, PKS_KS, 1 hit SM00823, PKS_PP, 1 hit |
SUPFAMi | SSF47336, SSF47336, 1 hit SSF50129, SSF50129, 1 hit SSF51735, SSF51735, 3 hits SSF52151, SSF52151, 1 hit SSF53335, SSF53335, 1 hit SSF53901, SSF53901, 1 hit SSF55048, SSF55048, 1 hit |
PROSITEi | View protein in PROSITE PS00606, B_KETOACYL_SYNTHASE, 1 hit PS50075, CARRIER, 1 hit PS00012, PHOSPHOPANTETHEINE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MOKB_MONPI | |
Accessioni | Q3S2U6Primary (citable) accession number: Q3S2U6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 11, 2016 |
Last sequence update: | October 11, 2005 | |
Last modified: | December 2, 2020 | |
This is version 91 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Fungal Protein Annotation Program |