Detail Information for IndEnz0010001008
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