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).
Sequence
MKATAASGTPTPIAVVGMGCRFAGGATDPQALWKLLEQGGSTWSKTPSSRFNVSGVYHPNGQRVGSMHVRGGHFLDQDPALFDASFFNMTSEVASCMDPQQRLILEVVYEALEAAGIPLESVAGSNTAVFSGAMYHDYQDSLHRNPETLPRYFITGNAGTMMSSRVSHFYDLRGPSVTVDTACSTTLTALHLAIQSIRAGEADMAIVAGSNLLLNSDVFVTMSNLGFLSPDGISYSFDPRANGYGRGEGVAAIILKALPRALRDGDPIRLVVRETALNQDGRTPAITGPSPEAQACLIRECYQKAGLDPRQTSYVEAHGTGTPTGDPLELAAISAAFQGQPLQIGSVKANLGHTEAASGLASVMKVALALEKGIVPPSARFLQPSKKLLEERKFQIPLSSQLWLPIDGICRASINNFGFGGANAHAIVERYDPAARISTSKPNGHIRPHDSHVEADRGKIYVLSAKDEHSCQEMISRLRDYLNRANPTDERQFLANMAYTLASRRSNLRWKAACRAHSLASLLSVLVSDGTRPRRSAEKARLGWVFTGQGAQWFAMGRELIEAYPVFKEALIECDGYIKGMGANWSIIDELRRGEAESRVNEAEFSLPLSTAIQVALVRLLWSWGIRPAAITSHSSGEVAAAYAVGAFSARSAIGISYIRGALIAKTQPAPTTKGGMLAVGLSRSEVGEYITRVQQQGEEYLVVGCINSPSNVTVSGDLSAVVRLEELLHADQIFARRLKVTQAFHSHHMQPLSGEFREALVEVFNADITDTTNACQDVVYASPKTGKRLDDCNHLRDPMHWVESMLFPVEFESSFREMCFDRKDQAQEVDKIIEIGPHGVLSGAIKQILQLPELAAFDISYLSCLSRGKSAVDTIQLLAMDLLQGGYPVDLNAVNFPYGCEAAEVQVLSDLPTYPWNHKTRYWKEPRISRAARQRKIPVHDLIGVQEPLCPPLLHLWQNVLRISDVPWIRDHVVGSRILFPGAGFISMVIDGLSQICNHDPETCGLSYILRDVDLAQALILPTDGDEGVDLRLTIRAADQKSLGMRDWQRFSVYSIAGDKDDWTEHCTGLIRAQVDHPVSSSSIQQKTNPPQWSRKMAPQDLWASLHATGICHGPLFQNIERIESDGQASWCTLTVADTVATMPHAYESQHIVHPTTLDSAIQAAYTVLPFMGTLMKTAMVPSRIGGMKIPASFASLEPGDMLCAQAKIKNQGLSAFTTDVAVFNESDMDEEAGIELEGLTFQSLGAVISDSRRDLTENESTYSSWHWAPDITLTNSTWLERILSTGTQSQEIGVMLELRRCTVHFIQEAIENLTTEDVERLSGHLVKFYCWMQAQLACATNGELGQDSADWLRDSEQERQSLRSRVVAATNNGEMICRLGPKLSAILRGELDPLELMMDGQLLSRYYIRAIKWSRSNTQASELVRLCCHKNPRARILEIGGGTGGCTQLIVNALGPTKPVGRYDFTDVSAGFFEAARKRFSGWQDVMDFRKLDIEGDPEVQGFDCGSYDVVLACQVLHATSNMQRTLNNVRKLLKPGGKLILVETTRDQLDLFFTFGLLPGWWLSEEPERQLTPSLSPELWRSVLSATGFSGVDLEVRDCDSDEFYMISTMMSTATPGTPATTLNGPAEVLLVHAGSPPPMDWLQNLQVALGGKNSSITSLKALQGVSDLKGKMCVFLGEMDRTLLESVVSDDFTSLTSMLQYSQGTLWVTRGAAMASDDPRKALHLGLLRTLRNENHGRRFVSLDLDPLRDPWTAQSCDAIVNVLNAVGASHEKEFEYAERDGTIHVPRTFSDSSSSEKEDLVVLEPFQNETRLVRLDVQTPGLLDSLHFKLCSADEAWSSELPEDWVEIEPRAFGLNFRDIMVAMGQLESNRVMGFECAGVVTRLSKAATTGAGGLAIGDRVCALMKGHWASRVRTARTNVICIPGTLSFEQAASIPLAFTTAYTSLYTVARLQRGEKVLIHGGAGGVGQAAIILAQLVGAEVFTTAGTHSKRNFLIDKFKLAPDHVFSSRDSGFIEGIRACTNGKGVDVVLNSLAGPLLQYSFDCLVNFGRFVEIGKKDLEQNSRLNMATFARNVSFSSIDILYWEEAKSAEIFRALTEIMRLLEQKTIDLIGPISEYPMSAIEKAFRTMQSGQHVGKLVVATAETDMIPVRRGTMPVALKLDASYLIVGGLGGIGRRICEWMVDHGARHLLILSRSGRTDPFVTGLQKRGCVVRIHSCDVADESQLHAVLQQCHEDNMPPIRGIIQAAMVLKDALVSQMTADDFHVALRPKVQGSWNLHKIASEVDFFIMLSSLVGVMGGAGQANYAAAGAFQDALAQHRVAQGKPAVTIDLGMVKSIGYVAETDPAVAERLARIGYQPMHEEEVLAVLERAMSPSSSSAPPSSNPTIPASPAVIVTGINTGPGPHFTNADWMQEARFAGIKYRDPLKDDRGGALSSSQPADEDSVRARLSRASTEEEATALVVQVMGHRLVTMFGLTESEMSATQTLSSVGVDSLVAIELRNWITAQLNVDISVFELMEGRTIAEVAEVVVKKYGVGSKV