MLCG_PENCI
ID MLCG_PENCI Reviewed; 362 AA.
AC Q8J0F9;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Compactin nonaketide synthase, enoyl reductase component {ECO:0000303|PubMed:12172803};
DE EC=2.3.1.- {ECO:0000305};
DE AltName: Full=Compactin biosynthesis protein G {ECO:0000303|PubMed:12172803};
DE AltName: Full=Compactin nonaketide synthase mlcG {ECO:0000305};
DE AltName: Full=Enoyl reductase {ECO:0000250|UniProtKB:Q9Y7D0};
GN Name=mlcG {ECO:0000303|PubMed:12172803};
OS Penicillium citrinum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=5077;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, AND FUNCTION.
RX PubMed=12172803; DOI=10.1007/s00438-002-0697-y;
RA Abe Y., Suzuki T., Ono C., Iwamoto K., Hosobuchi M., Yoshikawa H.;
RT "Molecular cloning and characterization of an ML-236B (compactin)
RT biosynthetic gene cluster in Penicillium citrinum.";
RL Mol. Genet. Genomics 267:636-646(2002).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=1010803; DOI=10.7164/antibiotics.29.1346;
RA Endo A., Kuroda M., Tsujita Y.;
RT "ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis
RT produced by Penicillium citrinium.";
RL J. Antibiot. 29:1346-1348(1976).
RN [3]
RP INDUCTION.
RX PubMed=12436257; DOI=10.1007/s00438-002-0755-5;
RA Abe Y., Ono C., Hosobuchi M., Yoshikawa H.;
RT "Functional analysis of mlcR, a regulatory gene for ML-236B (compactin)
RT biosynthesis in Penicillium citrinum.";
RL Mol. Genet. Genomics 268:352-361(2002).
CC -!- FUNCTION: Dehydrogenase; part of the gene cluster that mediates the
CC biosynthesis of compactin, also known as mevastatin or ML-236B, and
CC which acts as a potent competitive inhibitor of HMG-CoA reductase
CC (PubMed:12172803). Compactin biosynthesis is performed in two stages
CC (PubMed:12172803). The first stage is catalyzed by the nonaketide
CC synthase mlcA, which belongs to type I polyketide synthases and
CC catalyzes the iterative nine-step formation of the polyketide
CC (PubMed:12172803). This PKS stage is completed by the action of
CC dehydrogenase mlcG, which catalyzes the NADPH-dependent reduction of
CC the unsaturated tetra-, penta- and heptaketide intermediates that arise
CC during the mlcA-mediated biosynthesis of the nonaketide chain and leads
CC to dihydro-ML-236C carboxylate (PubMed:12172803). Covalently bound
CC dihydro-ML-236C carboxylate is released from mlcA by the mlcF esterase
CC (PubMed:12172803). Conversion of dihydro-ML-236C carboxylate into ML-
CC 236A carboxylate is subsequently performed with the participation of
CC molecular oxygen and P450 monoogygenase mlcC (PubMed:12172803).
CC Finally, mlcH performs the conversion of ML-236A carboxylate to ML-
CC 236B/compactin carboxylate through the addition of the side-chain
CC diketide moiety produced by the diketide synthase mlcB
CC (PubMed:12172803). {ECO:0000269|PubMed:12172803}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=20 H(+) + holo-[compactin nonaketide synthase] + 9 malonyl-CoA
CC + 11 NADPH = 9 CO2 + 9 CoA + dihydro-ML-236C-[compactin nonaketide
CC synthase] + 6 H2O + 11 NADP(+); Xref=Rhea:RHEA:57612, Rhea:RHEA-
CC COMP:14940, Rhea:RHEA-COMP:14941, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:142039; Evidence={ECO:0000305};
CC -!- PATHWAY: Polyketide biosynthesis. {ECO:0000269|PubMed:12172803}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- INDUCTION: Expression is induced at the beginning of the stationary
CC phase, which is consistent with the timing of compactin production
CC (PubMed:12172803). Expression is controlled by the ML-236B/compactin
CC cluster transcription regulator mlcR (PubMed:12436257).
CC {ECO:0000269|PubMed:12172803, ECO:0000269|PubMed:12436257}.
CC -!- BIOTECHNOLOGY: Compactin (also known as mevastatin or ML-236B) and the
CC intermediary metabolites Ml-236C and ML-236A are inhibitors of HMG-CoA
CC reductase involved in cholesterogenesis (PubMed:1010803). Their
CC hypocholesterolemic activity might be useful for lowering cholesterol
CC levels in the blood and reduce artherosclerosis and coronary heart
CC disease (PubMed:1010803). {ECO:0000269|PubMed:1010803}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; AB072893; BAC20562.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8J0F9; -.
DR SMR; Q8J0F9; -.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR InterPro; IPR013149; ADH-like_C.
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 Pfam; PF00107; ADH_zinc_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; Transferase.
FT CHAIN 1..362
FT /note="Compactin nonaketide synthase, enoyl reductase
FT component"
FT /id="PRO_0000436286"
FT BINDING 55..58
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 139..146
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 174..177
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 197..200
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 215
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 262..263
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 280
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 282..286
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 351..352
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 362 AA; 39600 MW; CDB2CC5EFBED0E0F CRC64;
MGVAMTEGSF IPPVKQTILT VNDKDEVVIW DDAPTPKLPA DQVYVRIHAV AVNPSDTKMR
GDFATPFACL GTDYAGTVVA VGSEITHVKV GDRVFGAQNE MCPRTPEQGA FSQYTITRGR
IWAKIPDSMT WEAAASLPAG ISTTGLAMKL LGMPLPYSET KPSKKTYVLI YGGSTATATI
AMQFMRLSGY TPIATCSHKN FDLAKKNGAE EVFDYRDADC AQKIRDYTRN NLAYALDCII
NVESTSTCYK AIGRAGGRYV ALNPFPEHAA TRKMVTSDWT LGPTIFGEGS TWPAPYGCEA
SEEVRLFGTE LWQVASRLVE EDKLYHHPLR VIDGGLEQVK QGMETVRNGE LSGEKIVVRF
SV
