| IED ID | IndEnz0016000086 |
| Enzyme Type ID | tyrosinase000086 |
| Protein Name |
Cyclopenase penL EC 1.-.-.- Penigequinolones biosynthesis cluster protein L |
| Gene Name | penL |
| Organism | Penicillium thymicola |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Penicillium Penicillium thymicola |
| Enzyme Sequence | MFALPVRKFHEPYYERKPSHAKKINGVYQTLTTAGMEVEDGIRKAKELLKENVNPELMRRALGIYLIHSRDAQRRKIVVPPLMSHVSFLSNRSIPPQTVSTTAGPTVVAGEVVTADTFQGPALLSYWREDYDLNDFHYYWHMMFPGTTVNVGGENIKLMDRPGEHFLQIVSQMVARYETEGLCWNLPLVRPWNQYDDILEHGYVPVPGLIEYYGGYPPFSSWYSVRNPDIPDLPQVDVSRKQMETWRDNIYEAIKNGYFWGKKQGTNAERTPLPLTPDNCMDLVGSVVDAEYLTLPPSPDGLSVDGDLYGNLHNYGHGNFAEISYQNYPTKAAQYGLMISNFGALRDPCFWPWHKHIQYFRRLASAKFPQDITAHRAHVRLSSLVICPQRKSTSISREDGITAFLGPPALNLLESKAKIGHEPYQWSVDIQSTRSSPPSEDSPQALTLRLFIAAGDLVNDYHSWIEMDRVTVHLTSKSTLTKVRLDTDSSIARKMGSYSELDPKSTSPWDRCRWPQHMMLPVGKVEGMPFVAFCMATDDTTAPRTRVPNSNTFEAIQSDQRLSDPLGMGYPFNRAWVQDVMDNAGKASIRQIISDAQTYPFMTTTTFRIFRATKMFQDSILNPYIPPASVTWFNTIKDYFLESDKTCMLYAYGYDLGNYDHVRLHSGAILDATSSKRMPLQMSPWSQENPDPNHPLWTPEMCDTFRAWMLNGCPKGTDSA |
| Enzyme Length | 720 |
| Uniprot Accession Number | A0A1B2CTB9 |
| 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 penigequinolones, potent insecticidal alkaloids that contain a highly modified 10-carbon prenyl group (PubMed:25859931). The first stage is catalyzed by the nonribosomal pepdide synthetase penN that condenses anthranilic acid and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin (By similarity). 4'-methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by the ketoglutarate-dependent dioxygenase penM through dehydrogenation to form a double bond between C-alpha and C-beta of the O-methyltyrosine side chain (By similarity). PenM also converts its first product methoxydehydrocyclopeptin to 4'-methoxycyclopenin (By similarity). The following conversion of 4'methoxycyclopenin into 4'-methoxyviridicatin is catalyzed by the cyclopenase penL (By similarity). 4'-methoxyviridicatin is the precursor of quinolone natural products, and is further converted to quinolinone B (Probable). The prenyltransferase penI 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 penH to yield conjugated aryl diene (PubMed:25859931). The delta(3') double bond then serves as the site of the second alkylation with DMAPP catalyzed by the prenyltransferase penG to yield a carbenium ion intermediate, which can be attacked by H(2)O to yield a styrenyl quinolone containing a C3'-hydroxyprenyl chain, or undergo cyclization to yield yaequinolones J1 and J2 (PubMed:25859931). The conversion of the styrenyl quinolone into the tetrahydrofuran-containing yaequinolone C is performed by the FAD-dependent monooxygenase penE and involves epoxidation of the terminal C7'-C8' olefin, followed by epoxide ring opening initiated by the C3' hydroxyl group (PubMed:25859931). The predicted cysteine hydrolase penJ acts as an epoxide hydrolase that enhances the rate of the 5-exo-tet cyclization step, increasing the yield of yaequinolone C (PubMed:25859931, PubMed:28114276). PenF catalyzes the cationic rearrangement of the epoxide formed by penE (before ring opening to produce yaequinolone C) into yaequinolone D (PubMed:28114276). Finally, the short-chain dehydrogenase/reductase (SDR)-like reductase penD, catalyzes both the dehydration of yaequinolone D and the reduction of the resulting oxonium to yield penigequinolone (PubMed:28114276). {ECO:0000250|UniProtKB:C8VJQ3, ECO:0000250|UniProtKB:Q5AR53, ECO:0000250|UniProtKB:Q5AR54, ECO:0000269|PubMed:25859931, ECO:0000269|PubMed:28114276, ECO:0000305|PubMed:25859931}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Secondary metabolite biosynthesis. {ECO:0000305|PubMed:25859931}.; PATHWAY: Alkaloid biosynthesis. {ECO:0000305|PubMed:25859931}.; PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:25859931}. |
| nucleotide Binding | |
| Features | Chain (1); Metal binding (3) |
| Keywords | Copper;Metal-binding;Monooxygenase;Oxidoreductase |
| Interact With | |
| Induction | |
| Subcellular Location | |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 81,904 |
| Kinetics | |
| Metal Binding | METAL 137; /note=Copper A; /evidence=ECO:0000250|UniProtKB:Q9ZP19; METAL 141; /note=Copper A; /evidence=ECO:0000250|UniProtKB:Q9ZP19; METAL 313; /note=Copper B; /evidence=ECO:0000250|UniProtKB:Q9ZP19 |
| Rhea ID | |
| Cross Reference Brenda |