Q3S2T9 · MOKA_MONPI
- ProteinLovastatin nonaketide synthase mokA
- GenemokA
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids3075 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score4/5
Function
function
Nonaketide synthase; 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
- holo-[lovastatin nonaketide synthase] + 9 malonyl-CoA + S-adenosyl-L-methionine + 11 NADPH + 19 H+ = dihydromonacolin L-[lovastatin nonaketide synthase] + S-adenosyl-L-homocysteine + 9 CO2 + 11 NADP+ + 9 CoA + 6 H2O
RHEA-COMP:10042 + 9 CHEBI:57384 + CHEBI:59789 + 11 CHEBI:57783 + 19 CHEBI:15378 = RHEA-COMP:10043 + CHEBI:57856 + 9 CHEBI:16526 + 11 CHEBI:58349 + 9 CHEBI:57287 + 6 CHEBI:15377
Cofactor
Note: Binds 1 phosphopantetheine covalently.
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 active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Active site | 222 | For beta-ketoacyl synthase activity | |||
Active site | 361 | For beta-ketoacyl synthase activity | |||
Active site | 408 | For beta-ketoacyl synthase activity | |||
Active site | 697 | For malonyltransferase activity | |||
Active site | 1029 | Proton acceptor; for dehydratase activity | |||
Active site | 1218 | Proton donor; for dehydratase activity | |||
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | 3-oxoacyl-[acyl-carrier-protein] synthase activity | |
Molecular Function | fatty acid synthase activity | |
Molecular Function | lovastatin nonaketide synthase activity | |
Molecular Function | methyltransferase activity | |
Molecular Function | oxidoreductase activity | |
Molecular Function | phosphopantetheine binding | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | methylation | |
Biological Process | toxin biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLovastatin nonaketide synthase mokA
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Monascus
Accessions
- Primary accessionQ3S2T9
Phenotypes & Variants
Disruption phenotype
Impairs the production of monacoline K (PubMed:18578535).
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Chain | PRO_0000436279 | 1-3075 | Lovastatin nonaketide synthase mokA | ||
Modified residue | 2531 | O-(pantetheine 4'-phosphoryl)serine | |||
Keywords
- PTM
Expression
Induction
Expression is controlled by the monacolin K cluster transcription regulator mokH (PubMed:19968298).
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 49-488 | Ketosynthase family 3 (KS3) | |||
Region | 603-945 | Acyl and malonyl transferase | |||
Region | 997-1133 | N-terminal hotdog fold | |||
Domain | 997-1311 | PKS/mFAS DH | |||
Region | 1029-1041 | Dehydratase-like | |||
Region | 1156-1311 | C-terminal hotdog fold | |||
Region | 1556-1594 | Methyltransferase | |||
Region | 2176-2470 | Beta-ketoacyl reductase | |||
Domain | 2492-2571 | Carrier | |||
Region | 2582-2624 | Disordered | |||
Compositional bias | 2586-2610 | Polar residues | |||
Region | 2633-2989 | Peptide synthetase elongation | |||
Family and domain databases
Sequence
- Sequence statusComplete
- Length3,075
- Mass (Da)338,037
- Last updated2005-10-11 v1
- Checksum6BDE751D492E9813
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Compositional bias | 2586-2610 | Polar residues | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DQ176595 EMBL· GenBank· DDBJ | ABA02239.1 EMBL· GenBank· DDBJ | Genomic DNA |