MOKC_MONPI
ID MOKC_MONPI Reviewed; 524 AA.
AC Q3S2T8;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Dihydromonacolin L monooxygenase mokC {ECO:0000250|UniProtKB:Q9Y7C8};
DE EC=1.14.14.124 {ECO:0000250|UniProtKB:Q9Y7C8};
DE EC=1.14.14.125 {ECO:0000250|UniProtKB:Q9Y7C8};
DE AltName: Full=Cytochrome P450 monooxygenase mokC {ECO:0000305};
DE AltName: Full=Dihydromonacolin L hydroxylase {ECO:0000250|UniProtKB:Q9Y7C8};
DE AltName: Full=Monacolin K biosynthesis protein C {ECO:0000303|PubMed:18578535};
DE AltName: Full=Monacolin L hydroxylase {ECO:0000250|UniProtKB:Q9Y7C8};
GN Name=mokC {ECO:0000303|PubMed:18578535};
OS Monascus pilosus (Red mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Monascus.
OX NCBI_TaxID=89488 {ECO:0000312|EMBL:ABA02241.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=18578535; DOI=10.1021/jf800595k;
RA Chen Y.P., Tseng C.P., Liaw L.L., Wang C.L., Chen I.C., Wu W.J., Wu M.D.,
RA Yuan G.F.;
RT "Cloning and characterization of monacolin K biosynthetic gene cluster from
RT Monascus pilosus.";
RL J. Agric. Food Chem. 56:5639-5646(2008).
RN [2]
RP FUNCTION.
RX PubMed=19693441; DOI=10.1007/s10529-009-0093-3;
RA Sakai K., Kinoshita H., Nihira T.;
RT "Identification of mokB involved in monacolin K biosynthesis in Monascus
RT pilosus.";
RL Biotechnol. Lett. 31:1911-1916(2009).
RN [3]
RP INDUCTION.
RX PubMed=19968298; DOI=10.1021/jf903139x;
RA Chen Y.-P., Yuan G.-F., Hsieh S.-Y., Lin Y.-S., Wang W.-Y., Liaw L.-L.,
RA Tseng C.-P.;
RT "Identification of the mokH gene encoding transcription factor for the
RT upregulation of monacolin K biosynthesis in Monascus pilosus.";
RL J. Agric. Food Chem. 58:287-293(2010).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=21821946; DOI=10.1271/bbb.110195;
RA Hong S.Y., Oh J.H., Lee I.;
RT "Simultaneous enrichment of deglycosylated ginsenosides and monacolin K in
RT red ginseng by fermentation with Monascus pilosus.";
RL Biosci. Biotechnol. Biochem. 75:1490-1495(2011).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of monakolin K, also known as lovastatin, and
CC which acts as a potent competitive inhibitor of HMG-CoA reductase
CC (PubMed:18578535). Monakolin K biosynthesis is performed in two stages
CC (PubMed:19693441). The first stage is catalyzed by the nonaketide
CC synthase mokA, which belongs to type I polyketide synthases and
CC catalyzes the iterative nine-step formation of the polyketide
CC (PubMed:18578535, PubMed:19693441). This PKS stage is completed by the
CC action of dehydrogenase mokE, which catalyzes the NADPH-dependent
CC reduction of the unsaturated tetra-, penta- and heptaketide
CC intermediates that arise during the mokA-mediated biosynthesis of the
CC nonaketide chain and leads to dihydromonacolin L (PubMed:19693441).
CC Covalently bound dihydromonacolin L is released from mokA by the mokD
CC esterase (By similarity). Conversion of dihydromonacolin L into
CC monacolin L and then monacolin J is subsequently performed with the
CC participation of molecular oxygen and P450 monoogygenase mokC
CC (PubMed:19693441). Finally, mokF performs the conversion of monacoline
CC J to monacoline K through the addition of the side-chain diketide
CC moiety (2R)-2-methylbutanoate produced by the diketide synthase mokB
CC (PubMed:19693441). {ECO:0000250|UniProtKB:Q0C8M2,
CC ECO:0000250|UniProtKB:Q9Y7C8, ECO:0000303|PubMed:18578535,
CC ECO:0000303|PubMed:19693441}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydromonacolin L carboxylate + O2 + reduced [NADPH--
CC hemoprotein reductase] = H(+) + 2 H2O + monacolin L carboxylate +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42368,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:79031, ChEBI:CHEBI:79044;
CC EC=1.14.14.124; Evidence={ECO:0000250|UniProtKB:Q9Y7C8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=monacolin L carboxylate + O2 + reduced [NADPH--hemoprotein
CC reductase] = H(+) + H2O + monacolin J carboxylate + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:29599, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:79035, ChEBI:CHEBI:79044; EC=1.14.14.125;
CC Evidence={ECO:0000250|UniProtKB:Q9Y7C8};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q02928};
CC Note=Binds 1 heme group per subunit. {ECO:0000250|UniProtKB:Q02928};
CC -!- PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis.
CC {ECO:0000250|UniProtKB:Q9Y7C8}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9Y7C8}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9Y7C8}.
CC -!- INDUCTION: Expression is controlled by the monacolin K cluster
CC transcription regulator mokH (PubMed:19968298).
CC {ECO:0000269|PubMed:19968298}.
CC -!- BIOTECHNOLOGY: Monacoline K acts as an inhibitor of HMG-CoA reductase
CC involved in cholesterogenesis (PubMed:21821946). Its
CC hypocholesterolemic activity might be useful for lowering cholesterol
CC levels in the blood and reduce artherosclerosis and coronary heart
CC disease (PubMed:21821946). {ECO:0000269|PubMed:21821946}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; DQ176595; ABA02241.1; -; Genomic_DNA.
DR AlphaFoldDB; Q3S2T8; -.
DR SMR; Q3S2T8; -.
DR UniPathway; UPA00875; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0008152; P:metabolic process; IEA:UniProt.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Heme; Iron; Membrane; Metal-binding;
KW Monooxygenase; Oxidoreductase; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..524
FT /note="Dihydromonacolin L monooxygenase mokC"
FT /id="PRO_0000436283"
FT TOPO_DOM 1..25
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 26..47
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 48..524
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT BINDING 467
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q02928"
FT CARBOHYD 396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 524 AA; 60541 MW; 9318DC27E147FA84 CRC64;
MTVPTDTVSR RLQSLAWSDI KQHAPWLPSS RTLVSGFLCL ILLQILYSRG RKSDLRVYNP
KKWWELTTMR AKREFDANAP AWIEAWFSKN DQPLRFIVDS GYCTILPSSM ADEFRKMKEL
CMYKFLGTDF HSHLPGFDGF KEVTRDAHLI TKVVMNQFQT QAAKYTKPLA DEASATIADI
FGDNKEWHTA PVYNECLDLV TRTVTFIMVG DKLAHNEEWL DIAKHHAVTM AIQARQLRLW
PVILRPIVHW LEPQGAKLRA QVRRARQLLE PIIQERRAEK AKCLAQGIEP PRYVDSIQWF
EDTAKGQWYD AAGAQLAMDF AGIYGTSDLM IGGLVDIVRH PHLIEPLRNE IRTVIGEEGW
TPASLYKLKL LDSCLKESQR VKPVECATMR SYALQNVTFS NGTFVPKGEL VAVAADRMSN
PEVWPEPKKY DPYRYMRLRE DPDKAFSAQL ENTNGNHIGF GWHPRACPGR FFASKEIKIM
LAFLLIRYDW KLVPNEPLQY YRHSFSVRIH PATKLMMRRR DEDL
