UniProtKB - Q9Y8A5 (LOVB_ASPTE)
Lovastatin nonaketide synthase, polyketide synthase component
lovB
Functioni
Lovastatin nonaketide synthase; part of the gene cluster that mediates the biosynthesis of lovastatin (also known as mevinolin, mevacor or monacolin K), a hypolipidemic inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) (PubMed:10334994, PubMed:12929390, PubMed:21495633, PubMed:23023987).
The first step in the biosynthesis of lovastatin is the production of dihydromonacolin L acid by the lovastatin nonaketide synthase lovB and the trans-acting enoyl reductase lovC via condensation of one acetyl-CoA unit and 8 malonyl-CoA units (PubMed:10334994, PubMed:10381407, PubMed:19900898, PubMed:23023987, PubMed:22733743).
Dihydromonacolin L acid is released from lovB by the thioesterase lovG (PubMed:23653178).
Next, dihydromonacolin L acid is oxidized by the dihydromonacolin L monooxygenase lovA twice to form monacolin J acid (PubMed:12929390, PubMed:21495633).
The 2-methylbutyrate moiety of lovastatin is synthesized by the lovastatin diketide synthase lovF via condensation of one acetyl-CoA unit and one malonyl-CoA unit (PubMed:19530726, PubMed:21069965).
Finally, the covalent attachment of this moiety to monacolin J acid is catalyzed by the transesterase lovD to yield lovastatin (PubMed:10334994, PubMed:17113998, PubMed:18988191, PubMed:19875080, PubMed:24727900).
LovD has broad substrate specificity and can also convert monacolin J to simvastatin using alpha-dimethylbutanoyl-S-methyl-3-mercaptopropionate (DMB-S-MMP) as the thioester acyl donor, and can also catalyze the reverse reaction and function as hydrolase in vitro (PubMed:19875080).
LovD has much higher activity with LovF-bound 2-methylbutanoate than with free diketide substrates (PubMed:21069965).
14 PublicationsCatalytic activityi
- 19 H+ + holo-[lovastatin nonaketide synthase] + 9 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine = 9 CO2 + 9 CoA + dihydromonacolin L-[lovastatin nonaketide synthase] + 6 H2O + 11 NADP+ + S-adenosyl-L-homocysteine3 PublicationsEC:2.3.1.1613 Publications
Cofactori
: lovastatin biosynthesis Pathwayi
This protein is involved in the pathway lovastatin biosynthesis, which is part of Polyketide biosynthesis.3 PublicationsView 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 | 181 | For beta-ketoacyl synthase activityPROSITE-ProRule annotation | 1 | |
Active sitei | 656 | For malonyltransferase activityPROSITE-ProRule annotation | 1 | |
Active sitei | 985 | For beta-hydroxyacyl dehydratase activityPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- 3-oxoacyl-[acyl-carrier-protein] synthase activity Source: InterPro
- acyltransferase activity, transferring groups other than amino-acyl groups Source: UniProtKB
- ATP binding Source: UniProtKB
- lovastatin nonaketide synthase activity Source: UniProtKB
- oxidoreductase activity Source: UniProtKB
- phosphopantetheine binding Source: InterPro
- S-adenosylmethionine-dependent methyltransferase activity Source: UniProtKB
GO - Biological processi
- fatty acid biosynthetic process Source: InterPro
- malonyl-CoA metabolic process Source: UniProtKB
- methylation Source: UniProtKB
- NADPH oxidation Source: UniProtKB
- polyketide biosynthetic process Source: UniProtKB
- S-adenosylmethionine metabolic process Source: UniProtKB
Keywordsi
Molecular function | Acyltransferase, Methyltransferase, Multifunctional enzyme, Oxidoreductase, Transferase |
Ligand | NADP, S-adenosyl-L-methionine |
Enzyme and pathway databases
BRENDAi | 2.3.1.161, 536 |
UniPathwayi | UPA00875 |
Names & Taxonomyi
Protein namesi | Recommended name: Lovastatin nonaketide synthase, polyketide synthase component (EC:2.3.1.1612 Publications)Short name: LNKS Alternative name(s): Lovastatin biosynthesis cluster protein B1 Publication |
Gene namesi | Name:lovBImported |
Organismi | Aspergillus terreus |
Taxonomic identifieri | 33178 [NCBI] |
Taxonomic lineagei | Eukaryota › Fungi › Dikarya › Ascomycota › Pezizomycotina › Eurotiomycetes › Eurotiomycetidae › Eurotiales › Aspergillaceae › Aspergillus › Aspergillus subgen. Circumdati |
Organism-specific databases
VEuPathDBi | FungiDB:ATEG_09961 |
Pathology & Biotechi
Biotechnological usei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000180288 | 1 – 3038 | Lovastatin nonaketide synthase, polyketide synthase componentAdd BLAST | 3038 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2498 | O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation | 1 |
Keywords - PTMi
Phosphopantetheine, PhosphoproteinInteractioni
Subunit structurei
Interacts with LovC.
1 PublicationProtein-protein interaction databases
DIPi | DIP-60051N |
IntActi | Q9Y8A5, 1 interactor |
Structurei
Secondary structure
3D structure databases
SMRi | Q9Y8A5 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 2463 – 2538 | CarrierPROSITE-ProRule annotation1 PublicationAdd BLAST | 76 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 11 – 450 | Ketosynthase (KS) domainSequence analysis1 PublicationAdd BLAST | 440 | |
Regioni | 562 – 889 | Malonyl-CoA:ACP transacylase (MAT) domainSequence analysis1 PublicationAdd BLAST | 328 | |
Regioni | 953 – 1263 | Dehydrogenase (DH) domainSequence analysis1 PublicationAdd BLAST | 311 | |
Regioni | 1443 – 1543 | Methyltransferase (CMet) domainSequence analysis1 PublicationAdd BLAST | 101 | |
Regioni | 2139 – 2437 | Ketoreductase (KR) domainSequence analysis1 PublicationAdd BLAST | 299 | |
Regioni | 2546 – 2602 | DisorderedSequence analysisAdd BLAST | 57 | |
Regioni | 2602 – 2952 | Inactive Condensation domain1 PublicationAdd BLAST | 351 |
Domaini
Family and domain databases
Gene3Di | 3.10.129.110, 1 hit 3.30.559.10, 1 hit 3.40.366.10, 1 hit 3.40.47.10, 1 hit 3.40.50.150, 1 hit |
InterProi | View protein in InterPro IPR001227, Ac_transferase_dom_sf IPR036736, ACP-like_sf IPR014043, Acyl_transferase IPR016035, Acyl_Trfase/lysoPLipase IPR023213, CAT-like_dom_sf IPR001242, Condensatn 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 IPR013968, PKS_KR IPR020806, PKS_PP-bd IPR009081, PP-bd_ACP IPR029063, SAM-dependent_MTases IPR016039, Thiolase-like |
Pfami | View protein in Pfam PF00698, Acyl_transf_1, 1 hit PF00668, Condensation, 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 PF14765, PS-DH, 1 hit |
SMARTi | View protein in SMART SM00827, PKS_AT, 1 hit SM00826, PKS_DH, 1 hit SM00825, PKS_KS, 1 hit SM00823, PKS_PP, 1 hit |
SUPFAMi | SSF47336, SSF47336, 1 hit SSF51735, SSF51735, 2 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 |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MAQSMYPNEP IVVVGSGCRF PGDANTPSKL WELLQHPRDV QSRIPKERFD
60 70 80 90 100
VDTFYHPDGK HHGRTNAPYA YVLQDDLGAF DAAFFNIQAG EAESMDPQHR
110 120 130 140 150
LLLETVYEAV TNAGMRIQDL QGTSTAVYVG VMTHDYETVS TRDLESIPTY
160 170 180 190 200
SATGVAVSVA SNRISYFFDW HGPSMTIDTA CSSSLVAVHL AVQQLRTGQS
210 220 230 240 250
SMAIAAGANL ILGPMTFVLE SKLSMLSPSG RSRMWDAGAD GYARGEAVCS
260 270 280 290 300
VVLKTLSQAL RDGDTIECVI RETGVNQDGR TTGITMPNHS AQEALIKATY
310 320 330 340 350
AQAGLDITKA EDRCQFFEAH GTGTPAGDPQ EAEAIATAFF GHEQVARSDG
360 370 380 390 400
NERAPLFVGS AKTVVGHTEG TAGLAGLMKA SFAVRHGVIP PNLLFDKISP
410 420 430 440 450
RVAPFYKNLR IPTEATQWPA LPPGQPRRAS VNSFGFGGTN AHAIIEEYME
460 470 480 490 500
PEQNQLRVSN NEDCPPMTGV LSLPLVLSAK SQRSLKIMME EMLQFLQSHP
510 520 530 540 550
EIHLHDLTWS LLRKRSVLPF RRAIVGHSHE TIRRALEDAI EDGIVSSDFT
560 570 580 590 600
TEVRGQPSVL GIFTGQGAQW PGMLKNLIEA SPYVRNIVRE LDDSLQSLPE
610 620 630 640 650
KYRPSWTLLD QFMLEGEASN VQYATFSQPL CCAVQIVLVR LLEAARIRFT
660 670 680 690 700
AVVGHSSGEI ACAFAAGLIS ASLAIRIAYL RGVVSAGGAR GTPGAMLAAG
710 720 730 740 750
MSFEEAQEIC ELDAFEGRIC VAASNSPDSV TFSGDANAID HLKGMLEDES
760 770 780 790 800
TFARLLKVDT AYHSHHMLPC ADPYMQALEE CGCAVADAGS PAGSVPWYSS
810 820 830 840 850
VDAENRQMAA RDVTAKYWKD NLVSPVLFSH AVQRAVVTHK ALDIGIEVGC
860 870 880 890 900
HPALKSPCVA TIKDVLSGVD LAYTGCLERG KNDLDSFSRA LAYLWERFGA
910 920 930 940 950
SSFDADEFMR AVAPDRPCMS VSKLLPAYPW DRSRRYWVES RATRHHLRGP
960 970 980 990 1000
KPHLLLGKLS EYSTPLSFQW LNFVRPRDIE WLDGHALQGQ TVFPAAGYIV
1010 1020 1030 1040 1050
MAMEAALMIA GTHAKQVKLL EILDMSIDKA VIFDDEDSLV ELNLTADVSR
1060 1070 1080 1090 1100
NAGEAGSMTI SFKIDSCLSK EGNLSLSAKG QLALTIEDVN PRTTSASDQH
1110 1120 1130 1140 1150
HLPPPEEEHP HMNRVNINAF YHELGLMGYN YSKDFRRLHN MQRADLRASG
1160 1170 1180 1190 1200
TLDFIPLMDE GNGCPLLLHP ASLDVAFQTV IGAYSSPGDR RLRCLYVPTH
1210 1220 1230 1240 1250
VDRITLVPSL CLATAESGCE KVAFNTINTY DKGDYLSGDI VVFDAEQTTL
1260 1270 1280 1290 1300
FQVENITFKP FSPPDASTDH AMFARWSWGP LTPDSLLDNP EYWATAQDKE
1310 1320 1330 1340 1350
AIPIIERIVY FYIRSFLSQL TLEERQQAAF HLQKQIEWLE QVLASAKEGR
1360 1370 1380 1390 1400
HLWYDPGWEN DTEAQIEHLC TANSYHPHVR LVQRVGQHLL PTVRSNGNPF
1410 1420 1430 1440 1450
DLLDHDGLLT EFYTNTLSFG PALHYARELV AQIAHRYQSM DILEIGAGTG
1460 1470 1480 1490 1500
GATKYVLATP QLGFNSYTYT DISTGFFEQA REQFAPFEDR MVFEPLDIRR
1510 1520 1530 1540 1550
SPAEQGFEPH AYDLIIASNV LHATPDLEKT MAHARSLLKP GGQMVILEIT
1560 1570 1580 1590 1600
HKEHTRLGFI FGLFADWWAG VDDGRCTEPF VSFDRWDAIL KRVGFSGVDS
1610 1620 1630 1640 1650
RTTDRDANLF PTSVFSTHAI DATVEYLDAP LASSGTVKDS YPPLVVVGGQ
1660 1670 1680 1690 1700
TPQSQRLLND IKAIMPPRPL QTYKRLVDLL DAEELPMKST FVMLTELDEE
1710 1720 1730 1740 1750
LFAGLTEETF EATKLLLTYA SNTVWLTENA WVQHPHQAST IGMLRSIRRE
1760 1770 1780 1790 1800
HPDLGVHVLD VDAVETFDAT FLVEQVLRLE EHTDELASST TWTQEPEVSW
1810 1820 1830 1840 1850
CKGRPWIPRL KRDLARNNRM NSSRRPIYEM IDSSRAPVAL QTARDSSSYF
1860 1870 1880 1890 1900
LESAETWFVP ESVQQMETKT IYVHFSCPHA LRVGQLGFFY LVQGHVQEGN
1910 1920 1930 1940 1950
REVPVVALAE RNASIVHVRP DYIYTEADNN LSEGGGSLMV TVLAAAVLAE
1960 1970 1980 1990 2000
TVISTAKCLG VTDSILVLNP PSICGQMLLH AGEEIGLQVH LATTSGNRSS
2010 2020 2030 2040 2050
VSAGDAKSWL TLHARDTDWH LRRVLPRGVQ ALVDLSADQS CEGLTQRMMK
2060 2070 2080 2090 2100
VLMPGCAHYR AADLFTDTVS TELHSGSRHQ ASLPAAYWEH VVSLARQGLP
2110 2120 2130 2140 2150
SVSEGWEVMP CTQFAAHADK TRPDLSTVIS WPRESDEATL PTRVRSIDAE
2160 2170 2180 2190 2200
TLFAADKTYL LVGLTGDLGR SLGRWMVQHG ACHIVLTSRN PQVNPKWLAH
2210 2220 2230 2240 2250
VEELGGRVTV LSMDVTSQNS VEAGLAKLKD LHLPPVGGIA FGPLVLQDVM
2260 2270 2280 2290 2300
LNNMELPMME MVLNPKVEGV RILHEKFSDP TSSNPLDFFV MFSSIVAVMG
2310 2320 2330 2340 2350
NPGQANYSAA NCYLQALAQQ RVASGLAAST IDIGAVYGVG FVTRAELEED
2360 2370 2380 2390 2400
FNAIRFMFDS VEEHELHTLF AEAVVAGRRA VHQQEQQRKF ATVLDMADLE
2410 2420 2430 2440 2450
LTTGIPPLDP ALKDRITFFD DPRIGNLKIP EYRGAKAGEG AAGSKGSVKE
2460 2470 2480 2490 2500
QLLQATNLDQ VRQIVIDGLS AKLQVTLQIP DGESVHPTIP LIDQGVDSLG
2510 2520 2530 2540 2550
AVTVGTWFSK QLYLDLPLLK VLGGASITDL ANEAAARLPP SSIPLVAATD
2560 2570 2580 2590 2600
GGAESTDNTS ENEVSGREDT DLSAAATITE PSSADEDDTE PGDEDVPRSH
2610 2620 2630 2640 2650
HPLSLGQEYS WRIQQGAEDP TVFNNTIGMF MKGSIDLKRL YKALRAVLRR
2660 2670 2680 2690 2700
HEIFRTGFAN VDENGMAQLV FGQTKNKVQT IQVSDRAGAE EGYRQLVQTR
2710 2720 2730 2740 2750
YNPAAGDTLR LVDFFWGQDD HLLVVAYHRL VGDGSTTENI FVEAGQLYDG
2760 2770 2780 2790 2800
TSLSPHVPQF ADLAARQRAM LEDGRMEEDL AYWKKMHYRP SSIPVLPLMR
2810 2820 2830 2840 2850
PLVGNSSRSD TPNFQHCGPW QQHEAVARLD PMVAFRIKER SRKHKATPMQ
2860 2870 2880 2890 2900
FYLAAYQVLL ARLTDSTDLT VGLADTNRAT VDEMAAMGFF ANLLPLRFRD
2910 2920 2930 2940 2950
FRPHITFGEH LIATRDLVRE ALQHARVPYG VLLDQLGLEV PVPTSNQPAP
2960 2970 2980 2990 3000
LFQAVFDYKQ GQAESGTIGG AKITEVIATR ERTPYDVVLE MSDDPTKDPL
3010 3020 3030
LTAKLQSSRY EAHHPQAFLE SYMSLLSMFS MNPALKLA
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF151722 Genomic DNA Translation: AAD39830.1 |
Genome annotation databases
KEGGi | ag:AAD39830 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF151722 Genomic DNA Translation: AAD39830.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
7CPX | electron microscopy | 2.91 | A/B | 1-3038 | [»] | |
7CPY | electron microscopy | 3.60 | A/B | 1-3038 | [»] | |
SMRi | Q9Y8A5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
DIPi | DIP-60051N |
IntActi | Q9Y8A5, 1 interactor |
Genome annotation databases
KEGGi | ag:AAD39830 |
Organism-specific databases
VEuPathDBi | FungiDB:ATEG_09961 |
Enzyme and pathway databases
UniPathwayi | UPA00875 |
BRENDAi | 2.3.1.161, 536 |
Family and domain databases
Gene3Di | 3.10.129.110, 1 hit 3.30.559.10, 1 hit 3.40.366.10, 1 hit 3.40.47.10, 1 hit 3.40.50.150, 1 hit |
InterProi | View protein in InterPro IPR001227, Ac_transferase_dom_sf IPR036736, ACP-like_sf IPR014043, Acyl_transferase IPR016035, Acyl_Trfase/lysoPLipase IPR023213, CAT-like_dom_sf IPR001242, Condensatn 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 IPR013968, PKS_KR IPR020806, PKS_PP-bd IPR009081, PP-bd_ACP IPR029063, SAM-dependent_MTases IPR016039, Thiolase-like |
Pfami | View protein in Pfam PF00698, Acyl_transf_1, 1 hit PF00668, Condensation, 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 PF14765, PS-DH, 1 hit |
SMARTi | View protein in SMART SM00827, PKS_AT, 1 hit SM00826, PKS_DH, 1 hit SM00825, PKS_KS, 1 hit SM00823, PKS_PP, 1 hit |
SUPFAMi | SSF47336, SSF47336, 1 hit SSF51735, SSF51735, 2 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | LOVB_ASPTE | |
Accessioni | Q9Y8A5Primary (citable) accession number: Q9Y8A5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 12, 2005 |
Last sequence update: | November 1, 1999 | |
Last modified: | May 25, 2022 | |
This is version 120 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Fungal Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structureDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references