MLCF_PENCI
ID MLCF_PENCI Reviewed; 251 AA.
AC Q8J0F8;
DT 11-MAY-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 37.
DE RecName: Full=Esterase mlcF {ECO:0000305};
DE EC=3.1.2.- {ECO:0000305};
DE AltName: Full=Compactin biosynthesis protein F {ECO:0000303|PubMed:12172803};
GN Name=mlcF {ECO:0000303|PubMed:12172803};
OS Penicillium citrinum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=5077 {ECO:0000312|EMBL:BAC20563.1};
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 FUNCTION.
RX PubMed=12242508; DOI=10.1007/s00438-002-0736-8;
RA Abe Y., Suzuki T., Mizuno T., Ono C., Iwamoto K., Hosobuchi M.,
RA Yoshikawa H.;
RT "Effect of increased dosage of the ML-236B (compactin) biosynthetic gene
RT cluster on ML-236B production in Penicillium citrinum.";
RL Mol. Genet. Genomics 268:130-137(2002).
RN [3]
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 [4]
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: Esterase; 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, PubMed:12242508). Compactin biosynthesis is performed
CC in two stages (PubMed:12172803). The first stage is catalyzed by the
CC nonaketide synthase mlcA, which belongs to type I polyketide synthases
CC and 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 ECO:0000269|PubMed:12242508}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydro-ML-236C-[compactin nonaketide synthase] + H2O =
CC dihydro-ML-236C carboxylate + H(+) + holo-[compactin nonaketide
CC synthase]; Xref=Rhea:RHEA:57616, Rhea:RHEA-COMP:14940, Rhea:RHEA-
CC COMP:14941, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:142039, ChEBI:CHEBI:142045; Evidence={ECO:0000305};
CC -!- PATHWAY: Polyketide biosynthesis. {ECO:0000305}.
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 LovG family. {ECO:0000305}.
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DR EMBL; AB072893; BAC20563.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8J0F8; -.
DR SMR; Q8J0F8; -.
DR ESTHER; penci-MLCF; FSH1.
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..251
FT /note="Esterase mlcF"
FT /id="PRO_0000436296"
FT ACT_SITE 126
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P38777"
FT ACT_SITE 193
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P38777"
FT ACT_SITE 221
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P38777"
SQ SEQUENCE 251 AA; 27952 MW; 4DFE65EA5EB3CDE8 CRC64;
MSPARITDFS PGKPRKALLC IHGAGCSAAI FRVQISKLRV ALKNEFEFVY ATAPFSSSPG
PGVLPVFQGM GPYYTWFQKH HDAVTNTTTP TVGDRVAAVI GPVQKTVQDW SITNPQAPIV
GIVAFSEGAL VATLLLHQQQ MGKLPWFPKM SIAVLICCFY SDEARDYMRA EAQDDDDKLI
INVPTLHLHG RQDFALQGSR QMVETHYLPQ NADVLEFQGK HNFPNRPSDV QETVKRFQQL
YQKVKMSGSF V
