| IED ID | IndEnz0010001615 |
| Enzyme Type ID | esterase001615 |
| Protein Name |
Clavatol synthase claF EC 2.3.1.- Clavatol biosynthesis cluster protein F Non-reducing polyketide synthase claF |
| Gene Name | claF |
| Organism | Penicillium crustosum (Blue mold fungus) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Penicillium Penicillium crustosum (Blue mold fungus) |
| Enzyme Sequence | MPSESYPRVNPKVFLFGPQALAFDAKLFTTLQSHLYDSWALDALSDLPIIWESLVKQVPKLQHVEGERLLRELHQGLQTGSLPDSLFPLPNILLSPLVVIVQLTQYLAFVRSGLPGLGDTDEIPQSVMQTSESLGLCTGILSAFAVSCASSIAKVQQYGAVAVRLSMLVGALVDAEEASPDTGSPAMSFSMSWNALESRTSVDEVLAEFPEAYISVFVDEKRATVTAPKESAPALLDKLRLSGAHVTEVALSGRFHWPKHREDAKQLIAFCDHDPRFQFPDASEIVLPTRLSTGGRLHEIALQEILLKPSEWLSLFGLVQSSHIDAGGANFVCFGSERCVPPTMIRKLGPLLIHISDVDLSTSALPSELLRSTSASPFDNLPDDQIAVIGMACHVPGAEDLDEYWRILTSGQSQHTRVPLERFSMKTAFRELEENRKWYGNFLRDYDTFDHKFFKKSAREMSSADPQHRLVLKLAYQAIEQSGYFGASHNSKHVGCYIGIGNNDYERNIACHPANAYSATGNLRSFAAGKVSHYFGWTGPSLTIDTACSSSGVAIHQACRAILHGECTSALAGGVNVLTSPEWFQNLAGASFLSPTGQCKPFDARGDGYCRGEGAGVVFLKRLSSAIADGDQVLGVIASTKVYQNQNCTAITVPNSISLAGLFGDVVEQARLEPQAISVVEAHGTGTPVGDPAEYDAVRRVFGGSIRSDTLSLMSVKGLLGHTEFASGIVSLVKILLMINEGFIPPQASFTSMSPALNAYHEDMINIATQLTPWNVDFRAALINNYGASGSNASMIITQAPKPRSSTSNPSPLSSSATSFPFWLCGIDSQSLRAYATKFRRFIHDNADSVKDLTVRNLSFQISRQSNRNLPRALIFSAASRNELEEKLLDYEQGGRSIAEIEVPPPRPVILCFGGQISTYVGLGKDVYNQATILRSHLDQCNTVCLSLGLGSIYPAIFQRSPILDTVELQTVLFAAQYSCARAWIDSGVKVTAVIGHSFGELTALCIAGAYSLADALRLISGRARLIRDKWGSDKGSMLALEADLAEVTALLSTSNKPDVSIACYNGPRSFTLAGSTESVQFIEELARSNQTFFGMKLKKLNVTNAFHSANVDPLISDLEALGREIQFNEPIIQVEAATETRSSPTRGSHFIAQHLRNPVYFNHAVQRLAEEYPAAIWLEAGSNSTITTMISRALGNSSSPHHFQSVHITSEESLPLLAEATTKLWKEGLNVSFWAHHPMEVSQHSLVILPPYQFEKARHWMDLKEVPEVKSSIDTTVQPPEPPKGLTTFIGFEDQAKQSARFRVNTTCDKFQQLTSANVALNTTAVTPGMLQIEISLDAIMNLQPDFKTYQFQPEVQGVSYHNALIDSNSTDLYLDAIAKDDGGLAWRWRLYGTDLGDRVTEFSSGSIVFLPASDPALKENFERLSRLSGKKRCASLLQGNGADDVLQGRNIYRAFEQVVNYAEPFRRVTKIAGKEDESAGYVSKAYTGETWMDPVLTECFCQVAGIFINLMTDASDLSKRGVYICDGISRWMHYPGLGSMTSAPDAWEVFAVHHHESETKYVSDVFAFDPRDGSLIEAILGISYRLVPMDSMRKLLTRGPQQESHFSTAAVSSKSTPVHAPTPTTTVSSTPSSLNSFQEKTIVKNVAKPPGPDISAKMCEIICNLSGLEPEEIEDDSDLVELGIDSLMAMELVREVDSAFKCTLQNDQLMELTDFASLVSCIRSTLGFDDEESGVGFERDSSVDTEAYILLEPNEPATNINGANGTVSFDHRDGNAVLSMSTLLDAFREIKWDTDDDIVKGQLGTYSKHVMPRSTELCIVYIVDAFEQLGCPIRSAAPGQVLTRVPYHPKHEKFMNMIIYGLLEKDARLIDINGSIITRTAVAPPTASADTLLSKLLHDEPVHAAEHKLAALIGQKFADLITDKEDGLKLIFGNPESREIAADMYSNSPVNTVWIKQLERFFERVLGRLPKDGQPICILEVGGGTGGTTSRIVPLLAKLGVPVKYTMTDISGSLIAAARKRFKKYPFMDFKPLNMESEPDAKFLQSQHIILATNCIHATRNLSVSLKNLHRILRPDGALIMLEMTEQVPWCDFIFGLLEGWWLFEDGRDYVLQPATYWEKVLQSVGYGHVDWTEGELPEARIQRLIIAHASGSRYDRGPKPPLASIPELTLPDISERRARIDAAVHKYTKDFVAPSQILSPAKLPSLSSGQCVLVTGATGSLGAHIVASLVQRPGIHTVVCLNRLSTTEATVRQQNSLQMRGISLDPTSLSKLKVIETDTSKPNLGLSPENYQYLIQNVTEIVHSAWPMSLTRPMRTYEPQFKIARGLIDLAREVAQHRPAPFKFGFQFISSSAVIANYPLLAGTPVVPEQSGTVESVPLTGYAEAKLATERILAETLYRFPDRFHVMAVRIAQITGSTSNGYWNPSEYMPFLIKSSQVLKILPELDGTLSWYPVNDVASVLGELLLSQSTTDLIYHIDNPSRQTWREMIAILARALDLGQKSIVPFGQWVNRVRGFRGSIADNPALQLIDFFEHYFVPMSCGGLVLDTTKSSQHSKTLQNQGPIDEDLMMKYIARWKESGFLNP |
| Enzyme Length | 2587 |
| Uniprot Accession Number | A0A481WQB6 |
| Absorption | |
| Active Site | ACT_SITE 137; /note=Nucleophile; for transacylase activity; /evidence=ECO:0000250|UniProtKB:A0A0K0MCJ4; ACT_SITE 256; /note=Proton donor/acceptor; for transacylase activity; /evidence=ECO:0000250|UniProtKB:A0A0K0MCJ4; ACT_SITE 548; /evidence=ECO:0000255|PROSITE-ProRule:PRU10022; ACT_SITE 1947; /note=For methyltransferase activity; /evidence=ECO:0000250|UniProtKB:Q65Z23; ACT_SITE 2059; /note=For methyltransferase activity; /evidence=ECO:0000250|UniProtKB:Q65Z23; ACT_SITE 2085; /note=For methyltransferase activity; /evidence=ECO:0000250|UniProtKB:Q65Z23 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=acetyl-CoA + AH2 + H(+) + 3 malonyl-CoA + 2 S-adenosyl-L-methionine = A + clavatol + 3 CO2 + 4 CoA + H2O + 2 S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:70075, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:17499, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:188925; Evidence={ECO:0000269|PubMed:30811183};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70076; Evidence={ECO:0000269|PubMed:30811183}; |
| DNA Binding | |
| EC Number | 2.3.1.- |
| Enzyme Function | FUNCTION: Non-reducing polyketide synthase; part of the cla gene cluster that produces clavatol and ortho-quinone methide (PubMed:30811183). The clavatol biosynthesis cluster cla and the terrestric acid cluster tra are both involved in the production of peniphenones and penilactones (PubMed:30811183). The non-reducing PKS claF is responsible for the formation of clavatol from successive condensations of 3 malonyl-CoA units, presumably with a simple acetyl-CoA starter unit, and 2 methylation steps (PubMed:30811183). The esterase claE probably collaborates with claF by catalyzing the hydrolysis of ACP-bound acyl intermediates to free the ACP from stalled intermediates (By similarity). The clavatol oxidase claD then converts clavatol to hydroxyclavatol (PubMed:30811183). Spontaneous dehydration of hydroxyclavatol leads to the accumulation of the highly active ortho-quinone methide (PubMed:30811183, PubMed:31860310). On the other hand, the PKS-NRPS hybrid traA is involved in the formation of crustosic acid, with the help of traB and traD (PubMed:30811183). The polyketide synthase module (PKS) of traA is responsible for the synthesis of the polyketide backbone via the condensation of an acetyl-CoA starter unit with 3 malonyl-CoA units (PubMed:30811183). The downstream nonribosomal peptide synthetase (NRPS) module then amidates the carboxyl end of the polyketide with L-malic acid (PubMed:30811183). Because traA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase traG (By similarity). Crustosic acid undergoes decarboxylation and isomerization to the terrestric acid, catalyzed by the 2-oxoglutarate-dependent dioxygenase traH (PubMed:30811183). Both acids are further converted to the 2 gamma-butyrolactones (R)-5-methyltetronic acid and (S)-5-carboxylmethyltetronic acid, with involvement of the cytochrome P450 monooxygenase claJ (PubMed:30811183). Spontaneous addition of the methide to these gamma-butyrolactones leads to peniphenone D and penilactone D, which undergo again stereospecific attacking by methide to give penilactones A and B (PubMed:30811183, PubMed:31860310). {ECO:0000250|UniProtKB:A0A0E0RXA7, ECO:0000250|UniProtKB:A0A161CKG1, ECO:0000269|PubMed:30811183, ECO:0000269|PubMed:31860310}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Secondary metabolite biosynthesis. {ECO:0000269|PubMed:30811183}. |
| nucleotide Binding | |
| Features | Active site (6); Chain (1); Domain (1); Modified residue (1); Region (6) |
| Keywords | Acyltransferase;Methyltransferase;Multifunctional enzyme;NADP;Phosphopantetheine;Phosphoprotein;Transferase |
| Interact With | |
| Induction | |
| Subcellular Location | |
| Modified Residue | MOD_RES 1688; /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 | 284,308 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:70075; RHEA:70076 |
| Cross Reference Brenda |