UniProtKB - Q9Y7D5 (LOVF_ASPTE)
Protein
Lovastatin diketide synthase lovF
Gene
lovF
Organism
Aspergillus terreus
Status
Functioni
Lovastatin diketide 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). 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: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).13 Publications
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-homocysteine2 PublicationsEC:2.3.1.2442 Publications
Cofactori
pantetheine 4'-phosphate2 PublicationsNote: Binds 1 phosphopantetheine covalently.2 Publications
: 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 | 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
- oxidoreductase activity Source: UniProtKB
- phosphopantetheine binding Source: InterPro
- S-adenosylmethionine-dependent methyltransferase activity Source: UniProtKB
- transferase activity, transferring acyl groups other than amino-acyl groups 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
BioCyci | MetaCyc:MONOMER-18789 |
UniPathwayi | UPA00875 |
Names & Taxonomyi
Protein namesi | Recommended name: Lovastatin diketide synthase lovF1 Publication (EC:2.3.1.2442 Publications)Short name: LDKS1 Publication Alternative name(s): Lovastatin biosynthesis cluster protein F1 Publication |
Gene namesi | Name:lovF1 Publication |
Organismi | Aspergillus terreus |
Taxonomic identifieri | 33178 [NCBI] |
Taxonomic lineagei | Eukaryota › Fungi › Dikarya › Ascomycota › Pezizomycotina › Eurotiomycetes › Eurotiomycetidae › Eurotiales › Aspergillaceae › Aspergillus › Aspergillus subgen. Circumdati |
Pathology & Biotechi
Biotechnological usei
Lovastatin acts as a hypolipidemic agent that works as inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) which reduces HMG-CoA to mevalonate and is the key step in cholesterol biosynthesis (PubMed:6933445). Lovastatin, simvastatin and related compounds are widely used to treat hypercholesteremia and reduce the risk of cardiovascular disease (PubMed:6933445). Furthermore, statins such as lovastatin were found to be anticancer agents (PubMed:29236027, PubMed:29932104).3 Publications
Disruption phenotypei
Loss of lovastatin biosynthesis.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000430268 | 1 – 2532 | Lovastatin diketide synthase lovFAdd BLAST | 2532 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2490 | O-(pantetheine 4'-phosphoryl)serinePROSITE-ProRule annotation | 1 |
Keywords - PTMi
Phosphopantetheine, PhosphoproteinProteomic databases
PRIDEi | Q9Y7D5 |
Interactioni
Subunit structurei
Interacts with LovD.
1 PublicationFamily & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 2453 – 2530 | CarrierPROSITE-ProRule annotationAdd BLAST | 78 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 13 – 433 | Ketosynthase (KS) domainSequence analysis2 PublicationsAdd BLAST | 421 | |
Regioni | 545 – 870 | Malonyl-CoA:ACP transacylase (MAT) domainSequence analysis2 PublicationsAdd BLAST | 326 | |
Regioni | 941 – 1246 | Dehydrogenase (DH) domainSequence analysis2 PublicationsAdd BLAST | 306 | |
Regioni | 1423 – 1607 | Methyltransferase (CMet) domainSequence analysis2 PublicationsAdd BLAST | 185 | |
Regioni | 1825 – 2144 | Enoylreductase (ER) domainSequence analysis2 PublicationsAdd BLAST | 320 | |
Regioni | 2168 – 2340 | Ketoreductase (KR) domainSequence analysis2 PublicationsAdd BLAST | 173 |
Domaini
Multidomain protein; including a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain that reduces hydroxyl groups to enoyl groups; a methyltransferase (CMeT) domain responsible for the incorporation of methyl groups; an enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm.2 Publications
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 IPR013149, ADH_C 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 PF00107, ADH_zinc_N, 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, 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 PS00012, PHOSPHOPANTETHEINE, 1 hit |
i Sequence
Sequence statusi: Complete.
Q9Y7D5-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MTPLDAPGAP APIAMVGMGC RFGGGATDPQ KLWKLLEEGG SAWSKIPPSR
60 70 80 90 100
FNVGGVYHPN GQRVGSMHVR GGHFLDEDPA LFDASFFNMS TEVASCMDPQ
110 120 130 140 150
YRLILEVVYE ALEAAGIPLE QVSGSKTGVF AGTMYHDYQG SFQRQPEALP
160 170 180 190 200
RYFITGNAGT MLANRVSHFY DLRGPSVSID TACSTTLTAL HLAIQSLRAG
210 220 230 240 250
ESDMAIVAGA NLLLNPDVFT TMSNLGFLSS DGISYSFDSR ADGYGRGEGV
260 270 280 290 300
AAIVLKTLPD AVRDGDPIRL IVRETAINQD GRTPAISTPS GEAQECLIQD
310 320 330 340 350
CYQKAQLDPK QTSYVEAHGT GTRAGDPLEL AVISAAFPGQ QIQVGSVKAN
360 370 380 390 400
IGHTEAVSGL ASLIKVALAV EKGVIPPNAR FLQPSKKLLK DTHIQIPLCS
410 420 430 440 450
QSWIPTDGVR RASINNFGFG GANAHAIVEQ YGPFAETSIC PPNGYSGNYD
460 470 480 490 500
GNLGTDQAHI YVLSAKDENS CMRMVSRLCD YATHARPADD LQLLANIAYT
510 520 530 540 550
LGSRRSNFRW KAVCTAHSLT GLAQNLAGEG MRPSKSADQV RLGWVFTGQG
560 570 580 590 600
AQWFAMGREL IEMYPVFKEA LLECDGYIKE MGSTWSIIEE LSRPETESRV
610 620 630 640 650
DQAEFSLPLS TALQIALVRL LWSWNIQPVA VTSHSSGEAA AAYAIGALTA
660 670 680 690 700
RSAIGISYIR GALTARDRLA SVHKGGMLAV GLSRSEVGIY IRQVPLQSEE
710 720 730 740 750
CLVVGCVNSP SSVTVSGDLS AIAKLEELLH ADRIFARRLK VTQAFHSSHM
760 770 780 790 800
NSMTDAFRAG LTELFGADPS DAANASKDVI YASPRTGARL HDMNRLRDPI
810 820 830 840 850
HWVECMLHPV EFESAFRRMC LDENDHMPKV DRVIEIGPHG ALGGPIKQIM
860 870 880 890 900
QLPELATCDI PYLSCLSRGK SSLSTLRLLA SELIRAGFPV DLNAINFPRG
910 920 930 940 950
CEAARVQVLS DLPPYPWNHE TRYWKEPRIS QSARQRKGPV HDLIGLQEPL
960 970 980 990 1000
NLPLARSWHN VLRVSDLPWL RDHVVGSHIV FPGAGFVCMA VMGISTLCSS
1010 1020 1030 1040 1050
DHESDDISYI LRDVNFAQAL ILPADGEEGI DLRLTICAPD QSLGSQDWQR
1060 1070 1080 1090 1100
FLVHSITADK NDWTEHCTGL VRAEMDQPPS SLSNQQRIDP RPWSRKTAPQ
1110 1120 1130 1140 1150
ELWDSLHRVG IRHGPFFRNI TCIESDGRGS WCTFAIADTA SAMPHAYESQ
1160 1170 1180 1190 1200
HIVHPTTLDS AVQAAYTTLP FAGSRIKSAM VPARVGCMKI SSRLADLEAR
1210 1220 1230 1240 1250
DMLRAQAKMH SQSPSALVTD VAVFDEADPV GGPVMELEGL VFQSLGASLG
1260 1270 1280 1290 1300
TSDRDSTDPG NTCSSWHWAP DISLVNPGWL EKTLGTGIQE HEISLILELR
1310 1320 1330 1340 1350
RCSVHFIQEA MESLSVGDVE RLSGHLAKFY AWMQKQLACA QNGELGPESS
1360 1370 1380 1390 1400
SWTRDSEQAR CSLRSRVVAG STNGEMICRL GSVLPAILRR EVDPLEVMMD
1410 1420 1430 1440 1450
GHLLSRYYVD ALKWSRSNAQ ASELVRLCCH KNPRARILEI GGGTGGCTQL
1460 1470 1480 1490 1500
VVDSLGPNPP VGRYDFTDVS AGFFEAARKR FAGWQNVMDF RKLDIEDDPE
1510 1520 1530 1540 1550
AQGFVCGSYD VVLACQVLHA TSNMQRTLTN VRKLLKPGGK LILVETTRDE
1560 1570 1580 1590 1600
LDLFFTFGLL PGWWLSEEPE RQSTPSLSPT MWRSMLHTTG FNGVEVEARD
1610 1620 1630 1640 1650
CDSHEFYMIS TMMSTAVQAT PMSCSVKLPE VLLVYVDSST PMSWISDLQG
1660 1670 1680 1690 1700
EIRGRNCSVT SLQALRQVPP TEGQICVFLG EVEHSMLGSV TNDDFTLLTS
1710 1720 1730 1740 1750
MLQLAGGTLW VTQGATMKSD DPLKALHLGL LRTMRNESHG KRFVSLDLDP
1760 1770 1780 1790 1800
SRNPWTGDSR DAIVSVLDLI SMSDEKEFDY AERDGVIHVP RAFSDSINGG
1810 1820 1830 1840 1850
EEDGYALEPF QDSQHLLRLD IQTPGLLDSL HFTKRNVDTY EPDKLPDDWV
1860 1870 1880 1890 1900
EIEPRAFGLN FRDIMVAMGQ LESNVMGFEC AGVVTSLSET ARTIAPGLAV
1910 1920 1930 1940 1950
GDRVCALMNG HWASRVTTSR TNVVRIPETL SFPHAASIPL AFTTAYISLY
1960 1970 1980 1990 2000
TVARILPGET VLIHAGAGGV GQAAIILAQL TGAEVFTTAG SETKRNLLID
2010 2020 2030 2040 2050
KFHLDPDHVF SSRDSSFVDG IKTRTRGKGV DVVLNSLAGP LLQKSFDCLA
2060 2070 2080 2090 2100
RFGRFVEIGK KDLEQNSRLD MSTFVRNVSF SSVDILYWQQ AKPAEIFQAM
2110 2120 2130 2140 2150
SEVILLWERT AIGLIHPISE YPMSALEKAF RTMQSGQHVG KIVVTVAPDD
2160 2170 2180 2190 2200
AVLVRQERMP LFLKPNVSYL VAGGLGGIGR RICEWLVDRG ARYLIILSRT
2210 2220 2230 2240 2250
ARVDPVVTSL QERGCTVSVQ ACDVADESQL EAALQQCRAE EMPPIRGVIQ
2260 2270 2280 2290 2300
GAMVLKDALV SQMTADGFHA ALRPKVQGSW NLHRIASDVD FFVMLSSLVG
2310 2320 2330 2340 2350
VMGGAGQANY AAAGAFQDAL AEHRMAHNQP AVTIDLGMVQ SIGYVAETDS
2360 2370 2380 2390 2400
AVAERLQRIG YQPLHEEEVL DVLEQAISPV CSPAAPTRPA VIVTGINTRP
2410 2420 2430 2440 2450
GPHWAHADWM QEARFAGIKY RDPLRDNHGA LSLTPAEDDN LHARLNRAIS
2460 2470 2480 2490 2500
QQESIAVIME AMSCKLISMF GLTDSEMSAT QTLAGIGVDS LVAIELRNWI
2510 2520 2530
TAKFNVDISV FELMEGRTIA KVAEVVLQRY KA
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF141925 Genomic DNA Translation: AAD34559.1 |
Genome annotation databases
KEGGi | ag:AAD34559 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF141925 Genomic DNA Translation: AAD34559.1 |
3D structure databases
SMRi | Q9Y7D5 |
ModBasei | Search... |
Proteomic databases
PRIDEi | Q9Y7D5 |
Genome annotation databases
KEGGi | ag:AAD34559 |
Enzyme and pathway databases
UniPathwayi | UPA00875 |
BioCyci | MetaCyc:MONOMER-18789 |
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 IPR013149, ADH_C 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 PF00107, ADH_zinc_N, 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, 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 PS00012, PHOSPHOPANTETHEINE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | LOVF_ASPTE | |
Accessioni | Q9Y7D5Primary (citable) accession number: Q9Y7D5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 3, 2014 |
Last sequence update: | November 1, 1999 | |
Last modified: | December 2, 2020 | |
This is version 119 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Fungal Protein Annotation Program |