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-MAY-2023, entry version 58. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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:0016651; F:oxidoreductase activity, acting on NAD(P)H; IEA:InterPro. DR CDD; cd08249; enoyl_reductase_like; 1. DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR013154; ADH-like_N. DR InterPro; IPR011032; GroES-like_sf. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR020843; PKS_ER. DR InterPro; IPR047122; Trans-enoyl_RdTase-like. DR PANTHER; PTHR45348; HYPOTHETICAL OXIDOREDUCTASE (EUROFUNG); 1. DR PANTHER; PTHR45348:SF2; ZINC-TYPE ALCOHOL DEHYDROGENASE-LIKE PROTEIN C2E1P3.01; 1. DR Pfam; PF08240; ADH_N; 1. DR Pfam; PF13602; ADH_zinc_N_2; 1. DR SMART; SM00829; PKS_ER; 1. DR SUPFAM; SSF50129; GroES-like; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 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 //