| IED ID | IndEnz0016000030 |
| Enzyme Type ID | tyrosinase000030 |
| Protein Name |
Cyclopenase asqI EC 1.-.-.- 4'-methoxyviridicatin/aspoquinolone biosynthesis cluster protein asqI Aspoquinolone biosynthesis protein I |
| Gene Name | asqI AN9228 ANIA_11193 |
| Organism | Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Aspergillus Aspergillus subgen. Nidulantes Emericella nidulans (Aspergillus nidulans) Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) (Aspergillus nidulans) |
| Enzyme Sequence | MTCTLRDLNSLLEICCRCPAHNPSTAFAPTTKVRVSSDVRGIFALPVQKDHKPYNGLSPEHLETMKAVSLMLDAAGPKLEDGISKAKELLEERINPELMRDALGIYLTHSKDAQQRKIFPPPLKNHPFFSTKTRRPANVAGEICTADTLHGHALLSYWRDDYDLNDSHYYWHMVYRGAGGDNSKNVGDFDRHGEVFLYVHSQMVARYETESLCWSLPLVRPWNQYDDFLENGYAPISSLIEHYGGYPPFSTWYSIRNPDMPDTLNVTIPRARLEEWRDNIYAAIRKGQFETTSKDKPLVLTRDNCLNFVGGILDAQYPSLNKLLGGCSLDEERYGNLHNYGLGKFAEMAYRNKPGEKSPYGLTISNFGAPRDPCFWRWYKHLQYYGRLAATRYPQDITAHRAEVVLSNLVVRLQDRSSPHYLDGHITTFLGPPAVNFMESKAKLGHEPYEWNVQVKSCRRSPPSKENPQTLTLRLFIAAEDLMNDYHSWIEMDRATVQLTDESAITKVRLDTDSSVARKMGNYGEPDPRYASAVFRHGWPQNLMLPVGKVEGMPFVAFCIATDDGIPDPAPAPPFHHYHDPRGMGYPFNRAWTQLTEDSTGKASIRTIISNAELYPFITSTTFKIYRTTKFETKQIIQPTTVTWFNTIRGYFKDADRACMRSEYGYDLYNYDHVMLHADAILDATASKRMPLQMGKYTQDNPDPEHPLWTVKMCENFRAWLLNGCPKGTDPA |
| Enzyme Length | 732 |
| Uniprot Accession Number | C8VJQ3 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 1.-.-.- |
| Enzyme Function | FUNCTION: Cyclopenase; part of the gene cluster that mediates the biosynthesis of the aspoquinolone mycotoxins (PubMed:25251934, PubMed:30026518). The first stage is catalyzed by the nonribosomal pepdide synthetase asqK that condenses anthranilic acid and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin (PubMed:25251934). AsqK is also able to use anthranilic acid and L-phenylalanine as substrates to produce cyclopeptin, but at a tenfold lower rate (PubMed:25251934). 4'-methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by the ketoglutarate-dependent dioxygenase asqJ through dehydrogenation to form a double bond between C-alpha and C-beta of the O-methyltyrosine side chain (PubMed:25251934, PubMed:26553478). AsqJ also converts its first product 4'-methoxydehydrocyclopeptin to 4'-methoxycyclopenin (PubMed:25251934). AsqJ is a very unique dioxygenase which is capable of catalyzing radical-mediated dehydrogenation and epoxidation reactions sequentially on a 6,7-benzo-diazepinedione substrate in the 4'-methoxyviridicatin biosynthetic pathway (PubMed:25251934). AsqJ is also capable of converting cyclopeptin into dehydrocyclopeptin (PubMed:25251934). The following conversion of 4'-methoxycyclopenin into 4'-methoxyviridicatin is catalyzed by the cyclopenase asqI (PubMed:30026518). Cyclopenin can also be converted into viridicatin by asqI (PubMed:30026518). 4'-methoxyviridicatin is the precursor of quinolone natural products, and is further converted to quinolinone B (Probable). The prenyltransferase asqH1 then catalyzes the canonical Friedel-Crafts alkylation of quinolinone B with dimethylallyl cation to yield dimethylallyl quinolone, which is subjected to FAD-dependent dehydrogenation by the FAD-linked oxidoreductase asqF to yield conjugated aryl diene (By similarity). The delta(3') double bond then serves as the site of the second alkylation with DMAPP catalyzed by the prenyltransferase asqH2 to yield a carbenium ion intermediate, which can be attacked by H(2)O to yield a styrenyl quinolone containing a C3'-hydroxyprenyl chain (By similarity). The FAD-dependent monooxygenase asqG performs epoxidation of the terminal C7'-C8' olefin (PubMed:30026518). Finally, after dehydratation of the epoxide at C3 by asqC, the quinolone epoxide rearrangement protein asqO catalyzes an enzymatic 3-exo-tet cyclization to yield the cyclopropyl-THF ring system in aspoquinolone (PubMed:30026518). {ECO:0000250|UniProtKB:A0A1B2CTB2, ECO:0000250|UniProtKB:A0A1B2CTB7, ECO:0000269|PubMed:25251934, ECO:0000269|PubMed:26553478, ECO:0000269|PubMed:30026518, ECO:0000305|PubMed:30026518}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Secondary metabolite biosynthesis. {ECO:0000269|PubMed:30026518}.; PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:30026518}.; PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30026518}. |
| nucleotide Binding | |
| Features | Chain (1); Erroneous gene model prediction (1); Metal binding (3); Mutagenesis (7) |
| Keywords | 3D-structure;Metal-binding;Monooxygenase;Oxidoreductase;Reference proteome;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 5YY2; 5YY3; |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 83,554 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.068 mM for (-)-Cyclopeptin {ECO:0000269|PubMed:30026518}; KM=2.86 mM for 4'-methoxycyclopenin {ECO:0000269|PubMed:30026518}; |
| Metal Binding | METAL 168; /note="Zinc"; /evidence="ECO:0000269|PubMed:30026518, ECO:0007744|PDB:5YY2"; METAL 172; /note="Zinc"; /evidence="ECO:0000269|PubMed:30026518, ECO:0007744|PDB:5YY2"; METAL 200; /note="Zinc"; /evidence="ECO:0000269|PubMed:30026518, ECO:0007744|PDB:5YY2" |
| Rhea ID | |
| Cross Reference Brenda |