Q3S2U1 · MOKE_MONPI
- ProteinDehydrogenase mokE
- GenemokE
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids360 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Dehydrogenase; 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).
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.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 50-53 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 134-141 | substrate | |||
Binding site | 173-176 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 196-199 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 214 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 261-262 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 279 | NADP+ (UniProtKB | ChEBI) | |||
Binding site | 281-285 | substrate | |||
Binding site | 350-351 | NADP+ (UniProtKB | ChEBI) | |||
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | nucleotide binding | |
Molecular Function | oxidoreductase activity, acting on NAD(P)H |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDehydrogenase mokE
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Monascus
Accessions
- Primary accessionQ3S2U1
Phenotypes & Variants
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000436285 | 1-360 | Dehydrogenase mokE | ||
Expression
Induction
Expression is controlled by the monacolin K cluster transcription regulator mokH (PubMed:19968298).
Interaction
Subunit
Monomer.
Structure
Sequence
- Sequence statusComplete
- Length360
- Mass (Da)38,845
- Last updated2005-10-11 v1
- Checksum9C63B9ADD38679C7
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DQ176595 EMBL· GenBank· DDBJ | ABA02243.1 EMBL· GenBank· DDBJ | Genomic DNA |