MOKD_MONPI
ID MOKD_MONPI Reviewed; 263 AA.
AC Q3S2U0;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 25-MAY-2022, entry version 36.
DE RecName: Full=Esterase mokD {ECO:0000250|UniProtKB:Q0C8M2};
DE EC=3.1.2.31 {ECO:0000250|UniProtKB:Q0C8M2};
DE AltName: Full=Monacolin K biosynthesis protein D {ECO:0000303|PubMed:18578535};
GN Name=mokD {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:ABA02242.1};
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: Esterase; 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 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:0000269|PubMed:19693441, ECO:0000303|PubMed:18578535}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydromonacolin L-[lovastatin nonaketide synthase] + H2O =
CC dihydromonacolin L carboxylate + H(+) + holo-[lovastatin nonaketide
CC synthase]; Xref=Rhea:RHEA:11592, Rhea:RHEA-COMP:10042, Rhea:RHEA-
CC COMP:10043, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:79031, ChEBI:CHEBI:79032; EC=3.1.2.31;
CC Evidence={ECO:0000250|UniProtKB:Q0C8M2};
CC -!- PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis.
CC {ECO:0000250|UniProtKB:Q0C8M2}.
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 LovG family. {ECO:0000305}.
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DR EMBL; DQ176595; ABA02242.1; -; Genomic_DNA.
DR AlphaFoldDB; Q3S2U0; -.
DR SMR; Q3S2U0; -.
DR UniPathway; UPA00875; -.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR005645; FSH_dom.
DR Pfam; PF03959; FSH1; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Hydrolase.
FT CHAIN 1..263
FT /note="Esterase mokD"
FT /id="PRO_0000436295"
FT ACT_SITE 134
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P38777"
FT ACT_SITE 208
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P38777"
FT ACT_SITE 236
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P38777"
SQ SEQUENCE 263 AA; 28843 MW; 2601F67003675191 CRC64;
MRIQRTPAPP KAPRALLCVH GAGCSPAIFR VQLSKLRAAL REDFEFVYAT APFPSAPGPG
ILPTFEGLGP YYTWFEGSPS GAAAKGDNSN SNDSNSSPTV HDRLAAVHEP VRRAIAEWQT
QNPSIPIVGT VSFSEGALVT ALLLWQQQMG RIPWLPVMQV AMFICCWYQH EATQYMREEV
GCGGDGGIDG EKLVIRGVLS LHLQGRDDFA LAGSKMVVAQ HFVPGEAQVL EFAGRHHFPN
RPRDVLETVK RFRQLCVRAR VIG
