| IED ID | IndEnz0010001464 |
| Enzyme Type ID | esterase001464 |
| Protein Name |
Dihydromonacolin L- lovastatin nonaketide synthase thioesterase EC 3.1.2.31 Esterase lovG Lovastatin biosynthesis cluster protein G |
| Gene Name | lovG ATEG_09962 |
| Organism | Aspergillus terreus (strain NIH 2624 / FGSC A1156) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Aspergillus Aspergillus subgen. Circumdati Aspergillus terreus Aspergillus terreus (strain NIH 2624 / FGSC A1156) |
| Enzyme Sequence | MRYQASPALAKAPRALLCIHGAGCSPAIFRVQLSKLRAALREDFEFVYVTAPFPSSAGPGILPVFADLGPYYSWFESSSGNNNNGPSVGERLAAVHDPIRRTIVDWQTQHPHIPIVGAIGFSEGALVTTLLLWQQQMGRLPWLPRMSVAMLICPWYQDEASQYMRNEVMENHDDDHDSKDTEWQEELVIRIPTLHLQGRDDFALAGSKMLVARHFSPREAQVLEFAGQHQFPNRPRDVLEVINRFRKLCVTVQTLE |
| Enzyme Length | 256 |
| Uniprot Accession Number | Q0C8M2 |
| Absorption | |
| Active Site | ACT_SITE 122; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P38777; ACT_SITE 201; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P38777; ACT_SITE 229; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P38777 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=dihydromonacolin L-[lovastatin nonaketide synthase] + H2O = dihydromonacolin L carboxylate + H(+) + holo-[lovastatin nonaketide synthase]; Xref=Rhea:RHEA:11592, Rhea:RHEA-COMP:10042, Rhea:RHEA-COMP:10043, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:64479, ChEBI:CHEBI:79031, ChEBI:CHEBI:79032; EC=3.1.2.31; Evidence={ECO:0000269|PubMed:23653178}; |
| DNA Binding | |
| EC Number | 3.1.2.31 |
| Enzyme Function | FUNCTION: Esterase; part of the gene cluster that mediates the biosynthesis of lovastatin (also known as mevinolin, mevacor or monacolin K), a hypolipidemic inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) (PubMed:10334994, PubMed:12929390, PubMed:21495633). The first step in the biosynthesis of lovastatin is the production of dihydromonacolin L acid by the lovastatin nonaketide synthase lovB and the trans-acting enoyl reductase lovC via condensation of one acetyl-CoA unit and 8 malonyl-CoA units (PubMed:10334994, PubMed:10381407, PubMed:19900898, PubMed:22733743). Dihydromonacolin L acid is released from lovB by the thioesterase lovG (PubMed:23653178). Next, dihydromonacolin L acid is oxidized by the dihydromonacolin L monooxygenase lovA twice to form monacolin J acid (PubMed:12929390, PubMed:21495633). The 2-methylbutyrate moiety of lovastatin is synthesized by the lovastatin diketide synthase lovF via condensation of one acetyl-CoA unit and one malonyl-CoA unit (PubMed:19530726, PubMed:21069965). Finally, the covalent attachment of this moiety to monacolin J acid is catalyzed by the transesterase lovD to yield lovastatin (PubMed:10334994, PubMed:17113998, PubMed:18988191, PubMed:19875080, PubMed:24727900). LovD has broad substrate specificity and can also convert monacolin J to simvastatin using alpha-dimethylbutanoyl-S-methyl-3-mercaptopropionate (DMB-S-MMP) as the thioester acyl donor, and can also catalyze the reverse reaction and function as hydrolase in vitro (PubMed:19875080). LovD has much higher activity with LovF-bound 2-methylbutanoate than with free diketide substrates (PubMed:21069965). {ECO:0000269|PubMed:10334994, ECO:0000269|PubMed:10381407, ECO:0000269|PubMed:12929390, ECO:0000269|PubMed:17113998, ECO:0000269|PubMed:18988191, ECO:0000269|PubMed:19530726, ECO:0000269|PubMed:19875080, ECO:0000269|PubMed:19900898, ECO:0000269|PubMed:21069965, ECO:0000269|PubMed:21495633, ECO:0000269|PubMed:22733743, ECO:0000269|PubMed:23653178, ECO:0000269|PubMed:24727900}.; FUNCTION: Esterase that catalyzes the release of covalently bound dihydromonacolin L from LovB during lovastatin biosynthesis. {ECO:0000269|PubMed:23653178}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Polyketide biosynthesis; lovastatin biosynthesis. {ECO:0000269|PubMed:23653178}. |
| nucleotide Binding | |
| Features | Active site (3); Chain (1) |
| Keywords | Hydrolase;Reference proteome |
| Interact With | |
| Induction | |
| Subcellular Location | |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 28,932 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:11592 |
| Cross Reference Brenda |