Q3S2T9 · MOKA_MONPI

  • Protein
    Lovastatin nonaketide synthase mokA
  • Gene
    mokA
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    4/5

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).

Catalytic activity

Cofactor

pantetheine 4'-phosphate (UniProtKB | Rhea| CHEBI:47942 )

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).

Pathway

Polyketide biosynthesis; lovastatin biosynthesis.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site222For beta-ketoacyl synthase activity
Active site361For beta-ketoacyl synthase activity
Active site408For beta-ketoacyl synthase activity
Active site697For malonyltransferase activity
Active site1029Proton acceptor; for dehydratase activity
Active site1218Proton donor; for dehydratase activity

GO annotations

AspectTerm
Molecular Function3-oxoacyl-[acyl-carrier-protein] synthase activity
Molecular Functionfatty acid synthase activity
Molecular Functionlovastatin nonaketide synthase activity
Molecular Functionmethyltransferase activity
Molecular Functionoxidoreductase activity
Molecular Functionphosphopantetheine binding
Biological Processfatty acid biosynthetic process
Biological Processmethylation
Biological Processtoxin biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Lovastatin nonaketide synthase mokA
  • EC number
  • Alternative names
    • Monacolin K biosynthesis protein A

Gene names

    • Name
      mokA

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Monascus

Accessions

  • Primary accession
    Q3S2T9

Phenotypes & Variants

Disruption phenotype

Impairs the production of monacoline K (PubMed:18578535).

PTM/Processing

Features

Showing features for chain, modified residue.

Type
IDPosition(s)Description
ChainPRO_00004362791-3075Lovastatin nonaketide synthase mokA
Modified residue2531O-(pantetheine 4'-phosphoryl)serine

Keywords

Expression

Induction

Expression is controlled by the monacolin K cluster transcription regulator mokH (PubMed:19968298).

Structure

Family & Domains

Features

Showing features for domain, region, compositional bias.

Type
IDPosition(s)Description
Domain49-488Ketosynthase family 3 (KS3)
Region603-945Acyl and malonyl transferase
Region997-1133N-terminal hotdog fold
Domain997-1311PKS/mFAS DH
Region1029-1041Dehydratase-like
Region1156-1311C-terminal hotdog fold
Region1556-1594Methyltransferase
Region2176-2470Beta-ketoacyl reductase
Domain2492-2571Carrier
Region2582-2624Disordered
Compositional bias2586-2610Polar residues
Region2633-2989Peptide synthetase elongation

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    3,075
  • Mass (Da)
    338,037
  • Last updated
    2005-10-11 v1
  • Checksum
    6BDE751D492E9813
MYVGRIGATTYISRPADSRATPKVIKTQGSITTSNLTSLTTMAQSTYPNEPIVVVGSGCRFPGGANTPSKLWELLREPRDVRSKIPKERFDVDAFYHPDGKHHGRTNAPYAYMLQEDLRAFDGPFFNIQAGEAESMDPQQRLLLETVYEAVSDAGMRIQDLQGSSTAVYVGMMTHDYETVSTRDLESIPTYSATGVAVSVASNRISYFFDWHGPSMTIDTACSSSLVAVHLAVQQLRSGQSSMAIAAGANMILGPMTFVLESKLNMLSPSGRSRMWDAGADGYARGEAVCSVVLKTLSQALRDGDSIECVIRETGVNQDGRTTGITMPNHSAQEALIRATYSKAGLDITNPEDRCQFFEAHGTGTPAGDPQEAEAIATAFFGHKKEASDAENAETPLFVGSVKTVVGHTEGTAGLAGLMKASFAVQHGVIPPNLLFENISPRVAPFYSNLKIATETTPWPTIKPGQPRRVSVNSFGFGGTNAHAIIEEYIKSDQKVPASRQPVEYSDSPSTLNLPLVLSAKSQRSMKTTLESMVQFLQSNPEVNLRDLSWTLLRKRSILPFRRAIVGHSHEAIRAALEAAIEDGIVVSDFSADVKGKPSVLGVFTGQGAQWPGMLKELIVGSSYVRSIAEELDHSLQTLPEKYRPSWTILEQLMLEDEASNVRHASFSQPLCCAVQIVLVRLLKAAGIQFAAVVGHSSGEIACAFATGLISASLAIRIAHLRGVVSAEHAASASGGRGSMLAAGMSYEEAKELCELDAFESRICVAASNSPDSVTFSGDADAIEHLQGVLEDEATFARLLRVDTAYHSHHMLPCAAPYMQALEECGCAVADGDGQVEEGSWYSSVKDSNEPMGLADVTAEYWKDNLVSPVLFSQAVQRAAIMHRPLDVGIEVGCHPALKGPCLATIKDALSDVDLAYTGCLERGKNDMNAFSQALAYLWEQFGIPSLDADRFISTIAPERSCVSLSKQLPTYSWDHSRSYWTESRATRQHLRGPKPHLLLGKLSEYSTPLTFQWLNFVRPRDIEWLDGHALQGQVVFPAAGYIVMAMEAAMEIANSHQVQVQLLEILDMSIDKAVVFDDEDSLVELNLTAEVTSGIGKGDRMILSFIIDSCLSREGDLSTSAKGQLVVTLDEGHLQVTPDNEKQLLPPPEEEHPHMNRVNINSFYHELDLMGYDYSKDFRRLHSMRRADARASGILEFIPLNDEVHGRPLLLHPAPLDIAFQTVIGAYSSPGDRRLRCLYVPTHIDRIALVPSLCLATAASGCDKIAFNTINTYDKGDFLSGDIVAFDAEQTSLFHVENIVFKPFSPPTASTDHPIFAKWSWGPLTPETLLDNPNHWATAQDKEAIPIIERIVYFYIKLFLQQLTREDREQAAFHLQRQIVWCEQVVADAHEGRHQWYDAAWENDTEAQIEQLCARSSYHPHVRLVQRVGQNLLATIRSNGNPFDLMDHDGLLTEFYTNTLSFGPALHYAQDLVGQIAHRYQSMDILEIGAGTGGATKYVLATPQLGFNSYTYTDISTGFFEKAREQFAAFEDRMEFEPLDIRRSPAEQGFTEHVYDLIIASNVLHATPDLEKTMAHARSLLKPGGQMVILEITHRNHTRLGFIFGLFADWWAGIDDGRTMEPFVSFDRWDEILKHVGFSGIDSRTKDRDADLFPTSVFSTHAVNSTIDYLHKPLDAPVKDSYPPLVVVGGQTPKTQRILDEIKAVMPNRQIQLHQRLVDLLDAEDMQAKFTFVVLTELDEELFAGLTEDSFEAVKLLLMYAGNMLWLTENAWVKRPHQASTIGMLRSIRREHPDIGVHIMDVDSAENLDAHFLVEQVLRLEEDIDELAATTTWTQEPEVFWCNGRAWIPRLKHDKSRNNRMNSSRRQIFETLNPSKIPVALKKAAASSSYYLESAETWPVPGAVTAGDRKTVHVRLSHPHALRVGHLGFFYLVQGHVLKGDQALPVVALAERNASIVHVRSDYVHVLEDTAVSANNGSFILAAAAAVLAETVIHSAKSLGADASVLVLNAPGFCAQTLLRAARDSGLRVHLATTSSSTDPSPGADRCVRLHPRDTDRRLKQLLPRGTQAFFDLSTDPSSEGLTQRLPNVLIPSCVRHSTEYLLRDTASAGGKATLPAAYWERVASLANHSLSTHFKENDNASNGCQVLSCTDIVARNNKSRLNASTVISWPDDAALPARIRPIDTETLFAAEKTYLLVGLTGDLGRSLGRWMVLHGARRIVLTSRNPQVSPNWVAHVEELGGQVTVLSMDVTSEDSVDSGLAKLQDLKLPPIGGIAFGPLVLQDVMLKNMDLQMMEMVLKPKVEGARILHEKFSDPASSNPLDFFVMFSSIVAVMGNPGQANYSAANCYLQALAQRRCASGLAASTIDIGAVYGVGFVTRAELEEDFNAIRFMFDSVEEHELHSLFAEAVVSGRRAMHQQQQFKTVLDMADIELTTGIPPLDPTLKDRITFFDDARVGNFKIPERRGKAGDNAAGSKGSVKEQLLQATSLDQVRQIVIDGLSEKLRVTLQIPDGESVHPTIPLIDQGVDSLGAVTVGTWFSKQLYLDLPLLRVLGGASVADLADDAAARLPPSSIPLVAASEGGAETSDNDTSGPEGTDLSASTTITEPSSADEEDEKQEDDNDNSVLALHPLSLGQEYAWRLQKAADDSTIFNNTIGMFMTGSIDAKRLSKALRAVLRRHEIFRTGFAAVGNNADATSLAQIVFGRTKNKVQVIQVADRAGAEEGYRQLVQTQYDITAGDTLRLVDFFWGKDEHLFVVAYHRFVGDGSTTENIFVEASQLYGGVTLDKHVPQFADLATRQREALESGQMDADLAYWESMHHQPTGVVSPVLPRMLLGEDGLNSPNHARQPNSWKQHEAIARLDPMVAFRIRERSRKHKATPMQFYLAAYHVLLARLTGSSDFSIGLADTNRTNVDELAGMGFFANLLPLRFRNFVPHITFGEHLVATKDKVREAMQHARVPYGVLLERLGFEVPGATAETAEPAPLFQAVFDYKQGQAESGSIGSAKMTEVIATRERTPYDVVLEMSDDPTKDPLLTVKLQSSVYEVHHPRAFLESYISILSMFSMNPALKLA

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias2586-2610Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DQ176595
EMBL· GenBank· DDBJ
ABA02239.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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