| IED ID | IndEnz0010000666 |
| Enzyme Type ID | esterase000666 |
| Protein Name |
Dihydro-ML-236C monooxygenase mlcC EC 1.14.14.- Compactin biosynthesis protein C DihydroML-236B hydroxylase |
| Gene Name | mlcC |
| Organism | Penicillium citrinum |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Penicillium Penicillium citrinum |
| Enzyme Sequence | MLGQVLLTVESYQWVSTPQALVAVAVLLSLIAYRLRGRQSELQVYNPKKWWELTTMRARQDFDTYGPSWIEAWFSKNDKPLRFIVDSGYCTILPSSMADEFRKIKDMCMYKFLADDFHSHLPGFDGFKEICQDAHLVNKVVLNQLQTQAPKYTKPLATLADATIAKLFGKSEEWQTAPVYSNGLDLVTRTVTLIMVGDKICHNEEWLDIAKNHAVSVAVQARQLRVWPMLLRPLAHWFQPQGRKLRDQVRRARKIIDPEIQRRRAEKAACVAKGVQPPQYVDTMQWFEDTADGRWYDVAGAQLAMDFAGIYASTDLFVGALVDIARHPDLIQPLRQEIRTVIGEGGWTPASLFKLKLLDSCMKETQRIKPVECATMRSTALRDITLSNGLFIPKGELAAVAADRMNNPDVWENPENYDPYRFMRMREDPDKAFTAQLENTNGDHIGFGWNPRACPGRFFASKEIKILLAHILIQYDVKPVPGDDDKYYRHAFSVRMHPTTKLMVRRRNEDIPLPHDRC |
| Enzyme Length | 518 |
| Uniprot Accession Number | Q8J0F6 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=dihydro-ML-236C carboxylate + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + 2 H2O + ML-236C carboxylate + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:57620, 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:142045, ChEBI:CHEBI:142047; Evidence={ECO:0000305}; CATALYTIC ACTIVITY: Reaction=ML-236C carboxylate + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + ML-236A carboxylate + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:57632, 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:142047, ChEBI:CHEBI:142048; Evidence={ECO:0000305}; |
| DNA Binding | |
| EC Number | 1.14.14.- |
| Enzyme Function | FUNCTION: Dihydro-ML-236C carboxylate monooxygenase; 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). {ECO:0000269|PubMed:12172803, ECO:0000269|PubMed:12242508}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Polyketide biosynthesis. {ECO:0000305}. |
| nucleotide Binding | |
| Features | Chain (1); Metal binding (1); Topological domain (2); Transmembrane (1) |
| Keywords | Endoplasmic reticulum;Heme;Iron;Membrane;Metal-binding;Monooxygenase;Oxidoreductase;Signal-anchor;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | INDUCTION: Expression is induced at the beginning of the stationary phase, which is consistent with the timing of compactin production (PubMed:12172803). Expression is controlled by the ML-236B/compactin cluster transcription regulator mlcR (PubMed:12436257, PubMed:18667169). {ECO:0000269|PubMed:12172803, ECO:0000269|PubMed:12436257, ECO:0000269|PubMed:18667169}. |
| 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 | 59,444 |
| Kinetics | |
| Metal Binding | METAL 454; /note=Iron (heme axial ligand); /evidence=ECO:0000250|UniProtKB:Q02928 |
| Rhea ID | RHEA:57620; RHEA:57632 |
| Cross Reference Brenda |