Function
HMG-CoA reductase; 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 (PubMed:12172803, PubMed:12242508). Compactin biosynthesis is performed in two stages (PubMed:12172803). 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 (PubMed:12172803). 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 (PubMed:12172803). Covalently bound dihydro-ML-236C carboxylate is released from mlcA by the mlcF esterase (PubMed:12172803). Conversion of dihydro-ML-236C carboxylate into ML-236A carboxylate is subsequently performed with the participation of molecular oxygen and P450 monoogygenase mlcC (PubMed:12172803). 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 (PubMed:12172803). HMG-CoA reductase mlcD may act as a down-regulator of compactin production and is involved in conferring resistance to ML-236B/compactin (PubMed:12242508).
Sequence
MVASLLPSRFRGRESMNQQHPLRSGNRALTSTLQFLSKTACLHPIHTVCTIAILASTTYVGLLKDSFFHGPANVDKAEWGSLVEGSRSLITGPQNGWKWQSFDGDADVLGDFNHQALMTLVFPGSYGVASQAASPFLAPLPVNLSVIDLPSTSSPLTAYSKDKVFAFSVEYSSAPELVAAVQEIPNNSADLKLQETQLIEMERQMWIMKAARAHTKRSLAQWVHDTWTESLDLIKSAQTLDVVVMVLGYISMHLTFVSLFLSMKKLGSKVWLATSVLLSSTFAFLLGLDVAIRLGVPMSMRLLSEGLPFLVVIVGFEKSITLTRAVLSYAVQHRKPQKIQSDQGSVTAIAESTINYAVRSAIREKGYNIVCHYVVEILLLVIGAVLGIQGGLQHFCVLAALILFFDCLLLFTFYTAILSIKLEVNRLKRHINMRYALEDEGLSQRTAESVATSNDAQDSARTYLFGNDMKGSSVPKFKFWMVVGFLIVNLVNIGSTLFQASSSGSLSSISSWTESLSGSAIKPPLEPFKVAGSGLDELLFQARGRGQSTMVTVLAPIKYELEYPSIHRGTSQLHEYGVGGKMVGSLLTSLEDPVLSKWVFVALALSVALNSYLFKAARLGIKDPNLPSHPVDPVELDQAESFNAAQNQTPQIQSSLQAPQTRVFTPTTTDSDSDASLVLIKASLKVTKRAEGKTATSELPVSRTQIELDNLLKQNTISELNDEDVVALSLRGKVPGYALEKSLKDCTRAVKVRRSIISRTPATAELTSMLEHSKLPYENYAWERVLGACCENVIGYMPVPVGVAGPIVIDGKSYFIPMATTEGVLVASASRGSKAINLGGGAVTVLTGDGMTRGPCVKFDVLERAGAAKIWLDSDVGQTVMKEAFNSTSRFARLQSMRTTIAGTHLYIRFKTTTGDAMGMNMISKGVEHALNVMATEAGFSDMNIITLSGNYCTDKKPSALNWIDGRGKGIVAEAIIPANVVRDVLKSDVDSMVQLNISKNLIGSAMAGSVGGFNAQAANLAAAIFIATGQDPAQVVESANCITLMNNLRGSLQISVSMPSIEVGTLGGGTILEPQGAMLDMLGVRGSHPTTPGENARQLARIIGSAVLAGELSLCAALAAGHLVKAHMAHNRSAPASSAPSRSVSPSGGTRTVPVPNNALRPSAAATDRARR