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 08-MAY-2019, entry version 52. 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., RA Wu M.D., Yuan G.F.; RT "Cloning and characterization of monacolin K biosynthetic gene cluster RT from 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 RT Monascus 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., RA Liaw L.-L., 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 RT K in 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 CC 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 CC stages (PubMed:19693441). The first stage is catalyzed by the CC nonaketide synthase mokA, which belongs to type I polyketide CC synthases and catalyzes the iterative nine-step formation of the CC polyketide (PubMed:18578535, PubMed:19693441). This PKS stage is CC completed by the action of dehydrogenase mokE, which catalyzes the CC NADPH-dependent reduction of the unsaturated tetra-, penta- and CC heptaketide intermediates that arise during the mokA-mediated CC biosynthesis of the nonaketide chain and leads to dihydromonacolin CC L (PubMed:19693441). Covalently bound dihydromonacolin L is CC released from mokA by the mokD esterase (By similarity). CC Conversion of dihydromonacolin L into monacolin L and then CC monacolin J is subsequently performed with the participation of CC molecular oxygen and P450 monoogygenase mokC (PubMed:19693441). CC Finally, mokF performs the conversion of monacoline J to CC monacoline K through the addition of the side-chain diketide CC moiety (2R)-2-methylbutanoate produced by the diketide synthase CC mokB (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 CC reductase involved in cholesterogenesis (PubMed:21821946). Its CC hypocholesterolemic activity might be useful for lowering CC cholesterol levels in the blood and reduce artherosclerosis and CC coronary heart disease (PubMed:21821946). CC {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 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 Dehydrogenase mokE. FT /FTId=PRO_0000436285. FT NP_BIND 50 53 NADP. {ECO:0000250|UniProtKB:Q9Y7D0}. FT NP_BIND 173 176 NADP. {ECO:0000250|UniProtKB:Q9Y7D0}. FT NP_BIND 196 199 NADP. {ECO:0000250|UniProtKB:Q9Y7D0}. FT NP_BIND 261 262 NADP. {ECO:0000250|UniProtKB:Q9Y7D0}. FT NP_BIND 350 351 NADP. {ECO:0000250|UniProtKB:Q9Y7D0}. FT REGION 134 141 Substrate binding. {ECO:0000255}. FT REGION 281 285 Substrate binding. {ECO:0000255}. FT BINDING 214 214 NADP. {ECO:0000250|UniProtKB:Q9Y7D0}. FT BINDING 279 279 NADP; via carbonyl oxygen. FT {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 //