IED ID | IndEnz0010000730 |
Enzyme Type ID | esterase000730 |
Protein Name |
Dihydromonacolin L monooxygenase mokC EC 1.14.14.124 EC 1.14.14.125 Cytochrome P450 monooxygenase mokC Dihydromonacolin L hydroxylase Monacolin K biosynthesis protein C Monacolin L hydroxylase |
Gene Name | mokC |
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 | MTVPTDTVSRRLQSLAWSDIKQHAPWLPSSRTLVSGFLCLILLQILYSRGRKSDLRVYNPKKWWELTTMRAKREFDANAPAWIEAWFSKNDQPLRFIVDSGYCTILPSSMADEFRKMKELCMYKFLGTDFHSHLPGFDGFKEVTRDAHLITKVVMNQFQTQAAKYTKPLADEASATIADIFGDNKEWHTAPVYNECLDLVTRTVTFIMVGDKLAHNEEWLDIAKHHAVTMAIQARQLRLWPVILRPIVHWLEPQGAKLRAQVRRARQLLEPIIQERRAEKAKCLAQGIEPPRYVDSIQWFEDTAKGQWYDAAGAQLAMDFAGIYGTSDLMIGGLVDIVRHPHLIEPLRNEIRTVIGEEGWTPASLYKLKLLDSCLKESQRVKPVECATMRSYALQNVTFSNGTFVPKGELVAVAADRMSNPEVWPEPKKYDPYRYMRLREDPDKAFSAQLENTNGNHIGFGWHPRACPGRFFASKEIKIMLAFLLIRYDWKLVPNEPLQYYRHSFSVRIHPATKLMMRRRDEDL |
Enzyme Length | 524 |
Uniprot Accession Number | Q3S2T8 |
Absorption | |
Active Site | |
Activity Regulation | |
Binding Site | |
Calcium Binding | |
catalytic Activity | CATALYTIC ACTIVITY: Reaction=dihydromonacolin L carboxylate + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + 2 H2O + monacolin L carboxylate + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42368, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:79031, ChEBI:CHEBI:79044; EC=1.14.14.124; Evidence={ECO:0000250|UniProtKB:Q9Y7C8}; CATALYTIC ACTIVITY: Reaction=monacolin L carboxylate + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + monacolin J carboxylate + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:29599, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:79035, ChEBI:CHEBI:79044; EC=1.14.14.125; Evidence={ECO:0000250|UniProtKB:Q9Y7C8}; |
DNA Binding | |
EC Number | 1.14.14.124; 1.14.14.125 |
Enzyme Function | FUNCTION: Cytochrome P450 monooxygenase; 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 is 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:Q9Y7C8, ECO:0000303|PubMed:18578535, ECO:0000303|PubMed:19693441}. |
Temperature Dependency | |
PH Dependency | |
Pathway | PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis. {ECO:0000250|UniProtKB:Q9Y7C8}. |
nucleotide Binding | |
Features | Chain (1); Glycosylation (2); Metal binding (1); Topological domain (2); Transmembrane (1) |
Keywords | Endoplasmic reticulum;Glycoprotein;Heme;Iron;Membrane;Metal-binding;Monooxygenase;Oxidoreductase;Signal-anchor;Transmembrane;Transmembrane helix |
Interact With | |
Induction | INDUCTION: Expression is controlled by the monacolin K cluster transcription regulator mokH (PubMed:19968298). {ECO:0000269|PubMed:19968298}. |
Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9Y7C8}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9Y7C8}. |
Modified Residue | |
Post Translational Modification | |
Signal Peptide | |
Structure 3D | |
Cross Reference PDB | - |
Mapped Pubmed ID | - |
Motif | |
Gene Encoded By | |
Mass | 60,541 |
Kinetics | |
Metal Binding | METAL 467; /note=Iron (heme axial ligand); /evidence=ECO:0000250|UniProtKB:Q02928 |
Rhea ID | RHEA:42368; RHEA:29599 |
Cross Reference Brenda |