Q3S2U2 · MOKF_MONPI
- ProteinAcyltransferase mokF
- GenemokF
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids413 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Acyltransferase; part of the gene cluster that mediates the biosynthesis of monakolin K, also known as lovastatin, and which acts as a potent competitive inhibitor of HMG-CoA reductase (PubMed:18578535).
Monakolin K biosynthesis is performed in two stages (PubMed:19693441).
The first stage is catalyzed by the nonaketide synthase mokA, which belongs to type I polyketide synthases and catalyzes the iterative nine-step formation of the polyketide (PubMed:18578535, PubMed:19693441).
This PKS stage is completed by the action of dehydrogenase mokE, which catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the mokA-mediated biosynthesis of the nonaketide chain and leads to dihydromonacolin L (PubMed:19693441).
Covalently bound dihydromonacolin L is released from mokA by the mokD esterase (By similarity).
Conversion of dihydromonacolin L into monacolin L and then monacolin J is subsequently performed with the participation of molecular oxygen and P450 monoogygenase mokC (PubMed:19693441).
Finally, mokF performs the conversion of monacoline J to monacoline K through the addition of the side-chain diketide moiety (2R)-2-methylbutanoate produced by the diketide synthase mokB (PubMed:19693441).
Monakolin K biosynthesis is performed in two stages (PubMed:19693441).
The first stage is catalyzed by the nonaketide synthase mokA, which belongs to type I polyketide synthases and catalyzes the iterative nine-step formation of the polyketide (PubMed:18578535, PubMed:19693441).
This PKS stage is completed by the action of dehydrogenase mokE, which catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the mokA-mediated biosynthesis of the nonaketide chain and leads to dihydromonacolin L (PubMed:19693441).
Covalently bound dihydromonacolin L is released from mokA by the mokD esterase (By similarity).
Conversion of dihydromonacolin L into monacolin L and then monacolin J is subsequently performed with the participation of molecular oxygen and P450 monoogygenase mokC (PubMed:19693441).
Finally, mokF performs the conversion of monacoline J to monacoline K through the addition of the side-chain diketide moiety (2R)-2-methylbutanoate produced by the diketide synthase mokB (PubMed:19693441).
Catalytic activity
- monacolin J carboxylate + (S)-2-methylbutanoyl-[2-methylbutanoate polyketide synthase] = lovastatin carboxylate + holo-[2-methylbutanoate polyketide synthase]
Biotechnology
Monacoline K acts as an inhibitor of HMG-CoA reductase involved in cholesterogenesis (PubMed:21821946).
Its hypocholesterolemic activity might be useful for lowering cholesterol levels in the blood and reduce artherosclerosis and coronary heart disease (PubMed:21821946).
Its hypocholesterolemic activity might be useful for lowering cholesterol levels in the blood and reduce artherosclerosis and coronary heart disease (PubMed:21821946).
Pathway
Polyketide biosynthesis; lovastatin biosynthesis.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 93 | monacolin J (UniProtKB | ChEBI) | |||
Active site | 96 | Acyl-ester intermediate | |||
Binding site | 193 | monacolin J (UniProtKB | ChEBI) | |||
Binding site | 208 | monacolin J (UniProtKB | ChEBI) | |||
Binding site | 278 | monacolin J (UniProtKB | ChEBI) | |||
Binding site | 386 | 2-methylbutanoate (UniProtKB | ChEBI) | |||
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | acyltransferase activity | |
Molecular Function | hydrolase activity |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAcyltransferase mokF
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Monascus
Accessions
- Primary accessionQ3S2U2
Phenotypes & Variants
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000436287 | 1-413 | Acyltransferase mokF | ||
Expression
Induction
Expression is controlled by the monacolin K cluster transcription regulator mokH (PubMed:19968298).
Structure
Sequence
- Sequence statusComplete
- Length413
- Mass (Da)46,693
- Last updated2005-10-11 v1
- MD5 ChecksumD4095092141FD8793AA7440463C21862
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DQ176595 EMBL· GenBank· DDBJ | ABA02244.1 EMBL· GenBank· DDBJ | Genomic DNA |