MOKF_MONPI
ID MOKF_MONPI Reviewed; 413 AA.
AC Q3S2U2;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Acyltransferase mokF {ECO:0000305};
DE EC=2.3.1.238 {ECO:0000250|UniProtKB:Q9Y7D1};
DE AltName: Full=Lovastatin hydrolase {ECO:0000250|UniProtKB:Q9Y7D1};
DE AltName: Full=Monacolin K biosynthesis protein F {ECO:0000303|PubMed:18578535};
GN Name=mokF {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:ABA02244.1};
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: Acyltransferase; 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 -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase] +
CC monacolin J carboxylate = holo-[2-methylbutanoate polyketide
CC synthase] + lovastatin carboxylate; Xref=Rhea:RHEA:43064, Rhea:RHEA-
CC COMP:10260, Rhea:RHEA-COMP:10261, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:79035, ChEBI:CHEBI:79038, ChEBI:CHEBI:82764;
CC EC=2.3.1.238; Evidence={ECO:0000250|UniProtKB:Q9Y7D1};
CC -!- PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis.
CC {ECO:0000250|UniProtKB:Q9Y7D1}.
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 class-A beta-lactamase family.
CC {ECO:0000305}.
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DR EMBL; DQ176595; ABA02244.1; -; Genomic_DNA.
DR AlphaFoldDB; Q3S2U2; -.
DR SMR; Q3S2U2; -.
DR UniPathway; UPA00875; -.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.710.10; -; 1.
DR InterPro; IPR001466; Beta-lactam-related.
DR InterPro; IPR012338; Beta-lactam/transpept-like.
DR Pfam; PF00144; Beta-lactamase; 1.
DR SUPFAM; SSF56601; SSF56601; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Hydrolase; Transferase.
FT CHAIN 1..413
FT /note="Acyltransferase mokF"
FT /id="PRO_0000436287"
FT ACT_SITE 96
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D1"
FT BINDING 93
FT /ligand="monacolin J"
FT /ligand_id="ChEBI:CHEBI:79034"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D1"
FT BINDING 193
FT /ligand="monacolin J"
FT /ligand_id="ChEBI:CHEBI:79034"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D1"
FT BINDING 208
FT /ligand="monacolin J"
FT /ligand_id="ChEBI:CHEBI:79034"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D1"
FT BINDING 278
FT /ligand="monacolin J"
FT /ligand_id="ChEBI:CHEBI:79034"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D1"
FT BINDING 386
FT /ligand="2-methylbutanoate"
FT /ligand_id="ChEBI:CHEBI:48946"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D1"
SQ SEQUENCE 413 AA; 46693 MW; 7976C0F5C03C0349 CRC64;
MRQFLSSDRI NSEIPQEKSE MVGFSDIDNS SRQIKEMEAA FRSAVKTGQI PGAVIMARDH
SGRLNYTRCF GARTVVRDEC NRLPPMQVDT PCRLASATKL LTTIMALQCV ERGLVRLDET
VDRLLPDLSA MKVLEGFDAA GEPKMRERKG KITLKHLLTH TSGLSYVFLH PLLREYMAKG
HLQTAEKFGI QSRLAPPAVN DPGAEWIYGA NLDWTGKLVE RATGLDLEQY LQENICAPLN
ITDMTFKLQQ RPDLLARRAD QTHRNKADGR LRYDDSVYFR SDGDECFGGQ GVFSGPESYM
KVVHSLLQRD GRLLRPETVD LMFQPALDAQ TEKQMNQHMD ASPHINYGGP MPMVLRRSFG
LGGMIALEDL DGQKWRRKGC LTFGGGPNIV WVMLLSALRF VFFFFFFFFF CSS
