Protein: Compactin nonaketide synthase, polyketide synthase component (EC 2.3.1.-) (Compactin biosynthesis protein A) (Compactin nonaketide synthase mlcA) (Q8J0F7)
Organism: Penicillium citrinum
Function: Nonaketide synthase; part of the gene cluster that mediates the biosynthesis of compactin, also known as mevastatin or ML-236B, and which acts as a potent competitive inhibitor of HMG-CoA reductase. Compactin biosynthesis is performed in two stages. The first stage is catalyzed by the nonaketide synthase mlcA, which belongs to type I polyketide synthases and catalyzes the iterative nine-step formation of the polyketide. This PKS stage is completed by the action of dehydrogenase mlcG, which catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the mlcA-mediated biosynthesis of the nonaketide chain and leads to dihydro-ML-236C carboxylate. Covalently bound dihydro-ML-236C carboxylate is released from mlcA by the mlcF esterase. Conversion of dihydro-ML-236C carboxylate into ML-236A carboxylate is subsequently performed with the participation of molecular oxygen and P450 monoogygenase mlcC. Finally, mlcH performs the conversion of ML-236A carboxylate to ML-236B/compactin carboxylate through the addition of the side-chain diketide moiety produced by the diketide synthase mlcB.
Interaction partners:
Sequence:
MDQANYPNEPIVVVGSGCRFPGGVNTPSKLWELLKEPRDVQTKIPKERFDVDTFYSPDGTHPGRTNAPFAYLLQEDLRGFDASFFNIQAGEAETIDPQQRLLLETVYEAVSNAGLRIQGLQGSSTAVYVGMMTHDYETIVTRELDSIPTYSATGVAVSVASNRVSYFFDWHGPSMTIDTACSSSLAAVHLAVQQLRTGESTMAVAAGANLILGPMTFVMESKLNMLSPNGRSRMWDAAADGYARGEGVCSIVLKTLSQALRDGDSIECVIRETGINQDGRTTGITMPNHSAQEALIRATYAKAGLDITNPQERCQFFEAHGTGTPAGDPQEAEAIATAFFGHKDGTIDSDGEKDELFVGSIKTVLGHTEGTAGIAGLMKASFAVRNGVIPPNLLFEKISPRVAPFYTHLKIATEATEWPIVAPGQPRRVSVNSFGFGGTNAHAIIEEYMAPPHKPTAVVTEVTSDADACSLPLVLSSKSQRSMKATLENMLQFLETHDDVDMHDIAYTLLEKRSILPFRRAIAAHNKEVARAALEAAIADGEVVTDFRTDANDNPRVLGVFTGQGAQWPGMLKKLMVGMPFVRGILEELDNSLQTLPEKYRPTWTLYDQLMLEGDASNVRLASFSQPLCCAVQIVLVRLLAAAGIEFSAIVGHSSGEIACAFAAGFISATQAIRIAHLRGVVSAEHASSPSGQTGAMLAAGMSYDDAKELCELEAFEGRVCVAASNSPDSVTFSGDMDAIQHVEGVLEDESTFARILRVDKAYHSHHMHPCAAPYVKALLECDCAVADGQGNDSVAWFSAVHETSKQMTVQDVMPAYWKDNLVSPVLFSQAVQKAVITHRLIDVAIEIGAHPALKGPCLATIKDALAGVELPYTGCLARNVDDVDAFAGGLGYIWERFGVRSIDAEGFVQQVRPDRAVQNLSKSLPTYSWDHTRQYWAESRSTRQHLRGGAPHLLLGKLSSYSTASTFQWTNFIRPRDLEWLDGHALQGQTVFPAAGYIIMAMEAAMKVAGERAAQVQLLEILDMSINKAIVFEDENTSVELNLTAEVTSDNDADGQVTVKFVIDSCLAKESELSTSAKGQIVITLGEASPSSQLLPPPEEEYPQMNNVNIDFFYRELDLLGYDYSKDFRRLQTMRRADSKASGTLAFLPLKDELRNEPLLLHPAPLDIAFQTVIGAYSSPGDRRLRSLYVPTHVDRVTLIPSLCISAGNSGETELAFDTINTHDKGDFLSGDITVYDSTKTTLFQVDNIVFKPFSPPTASTDHRIFAKWVWGPLTPEKLLEDPATLIIARDKEDILTIERIVYFYIKSFLAQITPDDRQNADLHSQKYIEWCDQVQADARAGHHQWYQESWEEDTSVHIEQMCESNSSHPHVRLIQRVGKELISIVRGNGDPLDIMNRDGLFTEYYTNKLAFGSAIHVVQDLVSQIAHRYQSIDILEIGLGTGIATKRVLASPQLGFNSYTCTDISADVIGKAREQLSEFDGLMQFEALDINRSPAEQGFKPHSYDLIIASDVLHASSNFEEKLAHIRSLLKPGGHLVTFGVTHREPARLAFISGLFADRWTGEDETRALSASGSVDQWEHTLKRVGFSGVDSRTLDREDDLIPSVFSTHAVDATVERLYDPLSAPLKDSYPPLVVIGGESTKTERILNDMKAALPHRHIHSVKRLESVLDDPALQPKSTFVILSELDDEVFCNLEEDKFEAVKSLLFYAGRMMWLTENAWIDHPHQASTIGMLRTIKLENPDLGTHVFDVDTVENLDTKFFVEQLLRFEESDDQLLESITWTHEPEVYWCKGRAWVPRLKQDIARNDRMNSSRRPIFGNFNSSKTAIALKEARGASSSMYYLESTETCDSLEDARHAGKATVRVRYALPQAIRVGHLGYFHVVQGSILENTCEVPVVALAEKNGSILHVPRNYMHSLPDNMAEGEDSSFLLSTAAALLAETILSSAQSFGSDASILIMEPPIFCVKAILESAKTYGVQVHLATTLSDVKTIPAPWIRLHAKETDARLKHSLPTNMMAFFDLSTDRTAAGITNRLAKLLPPSCFMYSGDYLIRSTASTYKVSHVEDIPILEHSVAMAKNTVSASTVDDTEKVITATQILLPGQLSVNHNDQRFNLATVIDWKENEVSARICPIDSGNLFSNKKTYLLVGLTGDLGRSLCRWMILHGARHVVLTSRNPRLDPKWIANMEALGGDITVLSMDVANEDSVDAGLGKLVDMKLPPVAGIAFGPLVLQDVMLKNMDHQMMDMVLKPKVQGARILHERFSEQTGSKALDFFIMFSSIVAVIGNPGQSNYGAANAYLQALAQQRCARGLAGSTIDIGAVYGVGFVTRAEMEEDFDAIRFMFDSVEEHELHTLFAEAVVSDQRARQQPQRKTVIDMADLELTTGIPDLDPALQDRIIYFNDPRFGNFKIPGQRGDGGDNGSGSKGSIADQLKQATTLDQVRQIVIDGLSEKLRVTLQVSDGESVDPTIPLIDQGVDSLGAVTVGSWFSKQLYLDLPLLRVLGGASVADLADDAATRLPATSIPLLLQIGDSTGTSDSGASPTPTDSHDEASSATSTDASSAEEDEEQEDDNEQGGRKILRRERLSLGQEYSWRQQQMVKDHTIFNNTIGMFMKGTIDLDRLRRALKASLRRHEIFRTCFVTGDDYSSDLNGPVQVVLKNPENRVHFVQVNNAAEAEEEYRKLEKTNYSISTGDTLRLVDFYWGTDDHLLVIGYHRLVGDGSTTENLFNEIGQIYSGVKMQRPSTQFSDLAVQQRENLENGRMGDDIAFWKSMHSKVSSSAPTVLPIMNLINDPAANSEQQQIQPFTWQQYEAIARLDPMVAFRIKERSRKHKATPMQFYLAAYHVLLARLTGSKDITIGLAETNRSTMEEISAMGFFANVLPLRFDEFVGSKTFGEHLVATKDSVREAMQHARVPYGVILDCLGLNLPTSGEEPKTQTHAPLFQAVFDYKQGQAESGSIGNAKMTSVLASRERTPYDIVLEMWDDPTKDPLIHVKLQSSLYGPEHAQAFVDHFSSILTMFSMNPALKLA