| IED ID | IndEnz0010001008 |
| Enzyme Type ID | esterase001008 |
| Protein Name |
Lovastatin diketide synthase mokB EC 2.3.1.244 Monacolin K biosynthesis protein B |
| Gene Name | mokB |
| Organism | Monascus pilosus (Red mold) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Monascus Monascus pilosus (Red mold) |
| Enzyme Sequence | MKATAASGTPTPIAVVGMGCRFAGGATDPQALWKLLEQGGSTWSKTPSSRFNVSGVYHPNGQRVGSMHVRGGHFLDQDPALFDASFFNMTSEVASCMDPQQRLILEVVYEALEAAGIPLESVAGSNTAVFSGAMYHDYQDSLHRNPETLPRYFITGNAGTMMSSRVSHFYDLRGPSVTVDTACSTTLTALHLAIQSIRAGEADMAIVAGSNLLLNSDVFVTMSNLGFLSPDGISYSFDPRANGYGRGEGVAAIILKALPRALRDGDPIRLVVRETALNQDGRTPAITGPSPEAQACLIRECYQKAGLDPRQTSYVEAHGTGTPTGDPLELAAISAAFQGQPLQIGSVKANLGHTEAASGLASVMKVALALEKGIVPPSARFLQPSKKLLEERKFQIPLSSQLWLPIDGICRASINNFGFGGANAHAIVERYDPAARISTSKPNGHIRPHDSHVEADRGKIYVLSAKDEHSCQEMISRLRDYLNRANPTDERQFLANMAYTLASRRSNLRWKAACRAHSLASLLSVLVSDGTRPRRSAEKARLGWVFTGQGAQWFAMGRELIEAYPVFKEALIECDGYIKGMGANWSIIDELRRGEAESRVNEAEFSLPLSTAIQVALVRLLWSWGIRPAAITSHSSGEVAAAYAVGAFSARSAIGISYIRGALIAKTQPAPTTKGGMLAVGLSRSEVGEYITRVQQQGEEYLVVGCINSPSNVTVSGDLSAVVRLEELLHADQIFARRLKVTQAFHSHHMQPLSGEFREALVEVFNADITDTTNACQDVVYASPKTGKRLDDCNHLRDPMHWVESMLFPVEFESSFREMCFDRKDQAQEVDKIIEIGPHGVLSGAIKQILQLPELAAFDISYLSCLSRGKSAVDTIQLLAMDLLQGGYPVDLNAVNFPYGCEAAEVQVLSDLPTYPWNHKTRYWKEPRISRAARQRKIPVHDLIGVQEPLCPPLLHLWQNVLRISDVPWIRDHVVGSRILFPGAGFISMVIDGLSQICNHDPETCGLSYILRDVDLAQALILPTDGDEGVDLRLTIRAADQKSLGMRDWQRFSVYSIAGDKDDWTEHCTGLIRAQVDHPVSSSSIQQKTNPPQWSRKMAPQDLWASLHATGICHGPLFQNIERIESDGQASWCTLTVADTVATMPHAYESQHIVHPTTLDSAIQAAYTVLPFMGTLMKTAMVPSRIGGMKIPASFASLEPGDMLCAQAKIKNQGLSAFTTDVAVFNESDMDEEAGIELEGLTFQSLGAVISDSRRDLTENESTYSSWHWAPDITLTNSTWLERILSTGTQSQEIGVMLELRRCTVHFIQEAIENLTTEDVERLSGHLVKFYCWMQAQLACATNGELGQDSADWLRDSEQERQSLRSRVVAATNNGEMICRLGPKLSAILRGELDPLELMMDGQLLSRYYIRAIKWSRSNTQASELVRLCCHKNPRARILEIGGGTGGCTQLIVNALGPTKPVGRYDFTDVSAGFFEAARKRFSGWQDVMDFRKLDIEGDPEVQGFDCGSYDVVLACQVLHATSNMQRTLNNVRKLLKPGGKLILVETTRDQLDLFFTFGLLPGWWLSEEPERQLTPSLSPELWRSVLSATGFSGVDLEVRDCDSDEFYMISTMMSTATPGTPATTLNGPAEVLLVHAGSPPPMDWLQNLQVALGGKNSSITSLKALQGVSDLKGKMCVFLGEMDRTLLESVVSDDFTSLTSMLQYSQGTLWVTRGAAMASDDPRKALHLGLLRTLRNENHGRRFVSLDLDPLRDPWTAQSCDAIVNVLNAVGASHEKEFEYAERDGTIHVPRTFSDSSSSEKEDLVVLEPFQNETRLVRLDVQTPGLLDSLHFKLCSADEAWSSELPEDWVEIEPRAFGLNFRDIMVAMGQLESNRVMGFECAGVVTRLSKAATTGAGGLAIGDRVCALMKGHWASRVRTARTNVICIPGTLSFEQAASIPLAFTTAYTSLYTVARLQRGEKVLIHGGAGGVGQAAIILAQLVGAEVFTTAGTHSKRNFLIDKFKLAPDHVFSSRDSGFIEGIRACTNGKGVDVVLNSLAGPLLQYSFDCLVNFGRFVEIGKKDLEQNSRLNMATFARNVSFSSIDILYWEEAKSAEIFRALTEIMRLLEQKTIDLIGPISEYPMSAIEKAFRTMQSGQHVGKLVVATAETDMIPVRRGTMPVALKLDASYLIVGGLGGIGRRICEWMVDHGARHLLILSRSGRTDPFVTGLQKRGCVVRIHSCDVADESQLHAVLQQCHEDNMPPIRGIIQAAMVLKDALVSQMTADDFHVALRPKVQGSWNLHKIASEVDFFIMLSSLVGVMGGAGQANYAAAGAFQDALAQHRVAQGKPAVTIDLGMVKSIGYVAETDPAVAERLARIGYQPMHEEEVLAVLERAMSPSSSSAPPSSNPTIPASPAVIVTGINTGPGPHFTNADWMQEARFAGIKYRDPLKDDRGGALSSSQPADEDSVRARLSRASTEEEATALVVQVMGHRLVTMFGLTESEMSATQTLSSVGVDSLVAIELRNWITAQLNVDISVFELMEGRTIAEVAEVVVKKYGVGSKV |
| Enzyme Length | 2547 |
| Uniprot Accession Number | Q3S2U6 |
| Absorption | |
| Active Site | ACT_SITE 183; /note=For beta-ketoacyl synthase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022; ACT_SITE 635; /note=For malonyltransferase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022; ACT_SITE 973; /note=For beta-hydroxyacyl dehydratase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=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-homocysteine; Xref=Rhea:RHEA:42852, Rhea:RHEA-COMP:10260, Rhea:RHEA-COMP:10261, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:57856, ChEBI:CHEBI:58349, ChEBI:CHEBI:59789, ChEBI:CHEBI:64479, ChEBI:CHEBI:82764; EC=2.3.1.244; Evidence={ECO:0000269|PubMed:19693441}; |
| DNA Binding | |
| EC Number | 2.3.1.244 |
| Enzyme Function | FUNCTION: 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). {ECO:0000250|UniProtKB:Q0C8M2, ECO:0000250|UniProtKB:Q9Y7D5, ECO:0000269|PubMed:19693441, ECO:0000303|PubMed:18578535}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis. {ECO:0000269|PubMed:19693441}. |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Disulfide bond (1); Domain (1); Modified residue (1); Region (4) |
| Keywords | Acyltransferase;Disulfide bond;Methyltransferase;Multifunctional enzyme;NADP;Oxidoreductase;Phosphopantetheine;Phosphoprotein;S-adenosyl-L-methionine;Transferase |
| Interact With | |
| Induction | INDUCTION: Expression is controlled by the monacolin K cluster transcription regulator mokH (PubMed:19968298). {ECO:0000269|PubMed:19968298}. |
| Subcellular Location | |
| Modified Residue | MOD_RES 2501; /note=O-(pantetheine 4'-phosphoryl)serine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00258 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 278,173 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:42852 |
| Cross Reference Brenda |