MOKE_MONPI
ID MOKE_MONPI Reviewed; 360 AA.
AC Q3S2U1;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=Dehydrogenase mokE {ECO:0000303|PubMed:18578535};
DE EC=1.-.-.- {ECO:0000305};
DE AltName: Full=Enoyl reductase {ECO:0000250|UniProtKB:Q9Y7D0};
DE AltName: Full=Monacolin K biosynthesis protein E {ECO:0000303|PubMed:18578535};
GN Name=mokE {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:ABA02243.1};
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: Dehydrogenase; part of the gene cluster that mediates the
CC biosynthesis of monakolin K, also known as lovastatin, and which acts
CC 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:0000303|PubMed:18578535, ECO:0000303|PubMed:19693441}.
CC -!- PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis.
CC {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
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 zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; DQ176595; ABA02243.1; -; Genomic_DNA.
DR AlphaFoldDB; Q3S2U1; -.
DR SMR; Q3S2U1; -.
DR UniPathway; UPA00875; -.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF08240; ADH_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NADP; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..360
FT /note="Dehydrogenase mokE"
FT /id="PRO_0000436285"
FT BINDING 50..53
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 134..141
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 173..176
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 196..199
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 214
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 261..262
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 279
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 281..285
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 350..351
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 360 AA; 38845 MW; 9C63B9ADD38679C7 CRC64;
MTITFTLPPH QTALTVDEHD KVTIWDVAPC PSLPPDQVCV RVEAVALNPS DTKMRGQFAT
PYAFLGTDYA GTVVAVGSQV THIQVGDRVY GAQNEMCPRT PDQGAFSQYT VTRGRIWATV
PEGWSFEQAA SLPAGISTAG LAMKLLGLPL PDPNATTAPA LPKPVYVLVY GGSTATATIV
MQMLRLSGYI PIATCSPHNF DLAKKHGAED VFDYRDAGLA QTIRTYTKNN LRYALDCITN
VESTTLCFAA IGRAGGRYVS LNPFPEHAAT RKMVTADWTL GPTIFGEGST WPAPYGRPGS
EKDRAFGEEL WRVAARLVED GKIVHHPLRV IPGGFEAIKQ GMELVRTGQL SGEKVVVKLG
