| IED ID | IndEnz0010000776 |
| Enzyme Type ID | esterase000776 |
| Protein Name |
Compactin nonaketide synthase, polyketide synthase component EC 2.3.1.- Compactin biosynthesis protein A Compactin nonaketide synthase mlcA |
| Gene Name | mlcA pks4 |
| Organism | Penicillium citrinum |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Penicillium Penicillium citrinum |
| Enzyme Sequence | MDQANYPNEPIVVVGSGCRFPGGVNTPSKLWELLKEPRDVQTKIPKERFDVDTFYSPDGTHPGRTNAPFAYLLQEDLRGFDASFFNIQAGEAETIDPQQRLLLETVYEAVSNAGLRIQGLQGSSTAVYVGMMTHDYETIVTRELDSIPTYSATGVAVSVASNRVSYFFDWHGPSMTIDTACSSSLAAVHLAVQQLRTGESTMAVAAGANLILGPMTFVMESKLNMLSPNGRSRMWDAAADGYARGEGVCSIVLKTLSQALRDGDSIECVIRETGINQDGRTTGITMPNHSAQEALIRATYAKAGLDITNPQERCQFFEAHGTGTPAGDPQEAEAIATAFFGHKDGTIDSDGEKDELFVGSIKTVLGHTEGTAGIAGLMKASFAVRNGVIPPNLLFEKISPRVAPFYTHLKIATEATEWPIVAPGQPRRVSVNSFGFGGTNAHAIIEEYMAPPHKPTAVVTEVTSDADACSLPLVLSSKSQRSMKATLENMLQFLETHDDVDMHDIAYTLLEKRSILPFRRAIAAHNKEVARAALEAAIADGEVVTDFRTDANDNPRVLGVFTGQGAQWPGMLKKLMVGMPFVRGILEELDNSLQTLPEKYRPTWTLYDQLMLEGDASNVRLASFSQPLCCAVQIVLVRLLAAAGIEFSAIVGHSSGEIACAFAAGFISATQAIRIAHLRGVVSAEHASSPSGQTGAMLAAGMSYDDAKELCELEAFEGRVCVAASNSPDSVTFSGDMDAIQHVEGVLEDESTFARILRVDKAYHSHHMHPCAAPYVKALLECDCAVADGQGNDSVAWFSAVHETSKQMTVQDVMPAYWKDNLVSPVLFSQAVQKAVITHRLIDVAIEIGAHPALKGPCLATIKDALAGVELPYTGCLARNVDDVDAFAGGLGYIWERFGVRSIDAEGFVQQVRPDRAVQNLSKSLPTYSWDHTRQYWAESRSTRQHLRGGAPHLLLGKLSSYSTASTFQWTNFIRPRDLEWLDGHALQGQTVFPAAGYIIMAMEAAMKVAGERAAQVQLLEILDMSINKAIVFEDENTSVELNLTAEVTSDNDADGQVTVKFVIDSCLAKESELSTSAKGQIVITLGEASPSSQLLPPPEEEYPQMNNVNIDFFYRELDLLGYDYSKDFRRLQTMRRADSKASGTLAFLPLKDELRNEPLLLHPAPLDIAFQTVIGAYSSPGDRRLRSLYVPTHVDRVTLIPSLCISAGNSGETELAFDTINTHDKGDFLSGDITVYDSTKTTLFQVDNIVFKPFSPPTASTDHRIFAKWVWGPLTPEKLLEDPATLIIARDKEDILTIERIVYFYIKSFLAQITPDDRQNADLHSQKYIEWCDQVQADARAGHHQWYQESWEEDTSVHIEQMCESNSSHPHVRLIQRVGKELISIVRGNGDPLDIMNRDGLFTEYYTNKLAFGSAIHVVQDLVSQIAHRYQSIDILEIGLGTGIATKRVLASPQLGFNSYTCTDISADVIGKAREQLSEFDGLMQFEALDINRSPAEQGFKPHSYDLIIASDVLHASSNFEEKLAHIRSLLKPGGHLVTFGVTHREPARLAFISGLFADRWTGEDETRALSASGSVDQWEHTLKRVGFSGVDSRTLDREDDLIPSVFSTHAVDATVERLYDPLSAPLKDSYPPLVVIGGESTKTERILNDMKAALPHRHIHSVKRLESVLDDPALQPKSTFVILSELDDEVFCNLEEDKFEAVKSLLFYAGRMMWLTENAWIDHPHQASTIGMLRTIKLENPDLGTHVFDVDTVENLDTKFFVEQLLRFEESDDQLLESITWTHEPEVYWCKGRAWVPRLKQDIARNDRMNSSRRPIFGNFNSSKTAIALKEARGASSSMYYLESTETCDSLEDARHAGKATVRVRYALPQAIRVGHLGYFHVVQGSILENTCEVPVVALAEKNGSILHVPRNYMHSLPDNMAEGEDSSFLLSTAAALLAETILSSAQSFGSDASILIMEPPIFCVKAILESAKTYGVQVHLATTLSDVKTIPAPWIRLHAKETDARLKHSLPTNMMAFFDLSTDRTAAGITNRLAKLLPPSCFMYSGDYLIRSTASTYKVSHVEDIPILEHSVAMAKNTVSASTVDDTEKVITATQILLPGQLSVNHNDQRFNLATVIDWKENEVSARICPIDSGNLFSNKKTYLLVGLTGDLGRSLCRWMILHGARHVVLTSRNPRLDPKWIANMEALGGDITVLSMDVANEDSVDAGLGKLVDMKLPPVAGIAFGPLVLQDVMLKNMDHQMMDMVLKPKVQGARILHERFSEQTGSKALDFFIMFSSIVAVIGNPGQSNYGAANAYLQALAQQRCARGLAGSTIDIGAVYGVGFVTRAEMEEDFDAIRFMFDSVEEHELHTLFAEAVVSDQRARQQPQRKTVIDMADLELTTGIPDLDPALQDRIIYFNDPRFGNFKIPGQRGDGGDNGSGSKGSIADQLKQATTLDQVRQIVIDGLSEKLRVTLQVSDGESVDPTIPLIDQGVDSLGAVTVGSWFSKQLYLDLPLLRVLGGASVADLADDAATRLPATSIPLLLQIGDSTGTSDSGASPTPTDSHDEASSATSTDASSAEEDEEQEDDNEQGGRKILRRERLSLGQEYSWRQQQMVKDHTIFNNTIGMFMKGTIDLDRLRRALKASLRRHEIFRTCFVTGDDYSSDLNGPVQVVLKNPENRVHFVQVNNAAEAEEEYRKLEKTNYSISTGDTLRLVDFYWGTDDHLLVIGYHRLVGDGSTTENLFNEIGQIYSGVKMQRPSTQFSDLAVQQRENLENGRMGDDIAFWKSMHSKVSSSAPTVLPIMNLINDPAANSEQQQIQPFTWQQYEAIARLDPMVAFRIKERSRKHKATPMQFYLAAYHVLLARLTGSKDITIGLAETNRSTMEEISAMGFFANVLPLRFDEFVGSKTFGEHLVATKDSVREAMQHARVPYGVILDCLGLNLPTSGEEPKTQTHAPLFQAVFDYKQGQAESGSIGNAKMTSVLASRERTPYDIVLEMWDDPTKDPLIHVKLQSSLYGPEHAQAFVDHFSSILTMFSMNPALKLA |
| Enzyme Length | 3032 |
| Uniprot Accession Number | Q8J0F7 |
| Absorption | |
| Active Site | ACT_SITE 181; /note=For beta-ketoacyl synthase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022; ACT_SITE 654; /note=For malonyltransferase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022; ACT_SITE 985; /note=For beta-hydroxyacyl dehydratase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=20 H(+) + holo-[compactin nonaketide synthase] + 9 malonyl-CoA + 11 NADPH = 9 CO2 + 9 CoA + dihydro-ML-236C-[compactin nonaketide synthase] + 6 H2O + 11 NADP(+); Xref=Rhea:RHEA:57612, Rhea:RHEA-COMP:14940, Rhea:RHEA-COMP:14941, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:64479, ChEBI:CHEBI:142039; Evidence={ECO:0000305}; |
| DNA Binding | |
| EC Number | 2.3.1.- |
| Enzyme Function | FUNCTION: Nonaketide synthase; part of the gene cluster that mediates the biosynthesis of compactin, also known as mevastatin or ML-236B, and which acts as a potent competitive inhibitor of HMG-CoA reductase (PubMed:12172803, PubMed:12242508). Compactin biosynthesis is performed in two stages (PubMed:12172803). The first stage is catalyzed by the nonaketide synthase mlcA, which belongs to type I polyketide synthases and catalyzes the iterative nine-step formation of the polyketide (PubMed:12172803). This PKS stage is completed by the action of dehydrogenase mlcG, which catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the mlcA-mediated biosynthesis of the nonaketide chain and leads to dihydro-ML-236C carboxylate (PubMed:12172803). Covalently bound dihydro-ML-236C carboxylate is released from mlcA by the mlcF esterase (PubMed:12172803). Conversion of dihydro-ML-236C carboxylate into ML-236A carboxylate is subsequently performed with the participation of molecular oxygen and P450 monoogygenase mlcC (PubMed:12172803). Finally, mlcH performs the conversion of ML-236A carboxylate to ML-236B/compactin carboxylate through the addition of the side-chain diketide moiety produced by the diketide synthase mlcB (PubMed:12172803). {ECO:0000269|PubMed:12172803, ECO:0000269|PubMed:12242508}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Polyketide biosynthesis. {ECO:0000305}. |
| nucleotide Binding | |
| Features | Active site (3); Chain (1); Compositional bias (1); Domain (1); Modified residue (1); Region (6) |
| Keywords | Acyltransferase;Methyltransferase;Multifunctional enzyme;NADP;Oxidoreductase;Phosphopantetheine;Phosphoprotein;S-adenosyl-L-methionine;Transferase |
| Interact With | |
| Induction | INDUCTION: Expression is induced at the beginning of the stationary phase, which is consistent with the timing of compactin production (PubMed:12172803). Expression is controlled by the ML-236B/compactin cluster transcription regulator mlcR (PubMed:12436257, PubMed:18667169). {ECO:0000269|PubMed:12172803, ECO:0000269|PubMed:12436257, ECO:0000269|PubMed:18667169}. |
| Subcellular Location | |
| Modified Residue | MOD_RES 2480; /note=O-(pantetheine 4'-phosphoryl)serine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00258 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 334,041 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:57612 |
| Cross Reference Brenda |