| IED ID | IndEnz0010001335 |
| Enzyme Type ID | esterase001335 |
| Protein Name |
Probable esterase ATEG_07663 EC 3.1.2.- Azasperpyranone A biosynthesis cluster B protein ATEG_07663 |
| Gene Name | ATEG_07663 |
| Organism | Aspergillus terreus (strain NIH 2624 / FGSC A1156) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Pezizomycotina leotiomyceta Eurotiomycetes Eurotiomycetidae Eurotiales (green and blue molds) Aspergillaceae Aspergillus Aspergillus subgen. Circumdati Aspergillus terreus Aspergillus terreus (strain NIH 2624 / FGSC A1156) |
| Enzyme Sequence | MSPPRFSGRQDGRTDPTTALPRVLCLHGGGTNARIFRTQCRVIRAHLADSFRLVFADGPFPSGPGPDVTAVYGDWGPFRAWLPHPAVKDPDVDKIDECIAAAMAADDRAGATGAWVGLLGFSQGARVAASLLLRQQRHQQRQKASLGFAYGATNAISEYRFAVLFAGRGPLLDMGAGDDNTRPEAELLELPTIHVHGLQDPGLEMHRDLLRCCLGSSARLVQWDGDHRVPIRRKDVSAVAAEIRDLASRGILGDG |
| Enzyme Length | 255 |
| Uniprot Accession Number | Q0CF71 |
| Absorption | |
| Active Site | ACT_SITE 122; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P38777; ACT_SITE 200; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P38777; ACT_SITE 227; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P38777 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.1.2.- |
| Enzyme Function | FUNCTION: Probable esterase; part of the cluster B that mediates the biosynthesis of azasperpyranones, members of the azaphilone family that exhibit anti-cancer activities (PubMed:31908094). Azasperpyranones are synthesized by 2 clusters, A and B (PubMed:31908094). Cluster A is responsible for the production of the polyhydric phenol moiety while the azaphilonoid scaffold is produced by the cluster B (PubMed:31908094). The non-reducing polyketide synthase ATEG_03629 produces 5-methyl orsellinic acid, which is then reduced to 5-methyl orsellinic aldehyde by the NRPS-like protein ATEG_03630 (PubMed:24412543). 5-methyl orsellinic aldehyde is then first hydroxylated by the FAD-dependent monooxygenase ATEG_03635 and subsequently hydroxylated by the cytochrome P450 monooxygenase ATEG_03631 to produce the unstable polyhydric phenol precursor of azasperpyranones (PubMed:31908094). On the other hand, the polyketide synthase ATEG_07659 is responsible for producing the 3,5-dimethyloctadienone moiety from acetyl-CoA, three malonyl-CoA, and two S-adenosyl methionines (SAM) (Probable). The 3,5-dimethyloctadienone moiety is then loaded onto the SAT domain of ATEG_07661 and extended with four malonyl-CoA and one SAM, which leads to the formation of 2,4-dihydroxy-6-(5,7-dimethyl-2-oxo-trans-3-trans-5-nonadienyl)-3-methylbenzaldehyde (compound 8) after reductive release and aldol condensation (Probable). The FAD-dependent monooxygenase ATEG_07662 is the next enzyme in the biosynthesis sequence and hydroxylates the side chain at the benzylic position of compound 8 (Probable). In Aspergillus nidulans, afoF, the ortholog of the FAD-dependent oxygenase ATEG_07660, is the key enzyme for the biosynthesis of asperfuranone by catalyzing the hydroxylation at C-8 of to prevent the formation of a six-membered ring hemiacetal intermediate and thus facilitatings the formation of a five-membered ring to produce asperfuranone (Probable). In Aspergillus terreus, ATEG_07660 is probably not functional, which leads to the formation of the six-membered ring hemiacetal intermediate presperpyranone instead of asperfuranone (Probable). Finally, ATEG_03636 is involved in the condensation of the polyhydric phenol moiety produced by cluster A and the perasperpyranone precursor produced by cluster B, to yield azasperpyranone A (Probable). Further modifications of azasperpyranone A result in the production of derivatives, including azasperpyranone B to F (PubMed:31908094). {ECO:0000269|PubMed:24412543, ECO:0000269|PubMed:31908094, ECO:0000305|PubMed:31908094}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Chain (1) |
| Keywords | Hydrolase;Reference proteome |
| Interact With | |
| Induction | INDUCTION: Expression is induced by the azasperpyranone cluster A-specific transcription factor ATEG_07666 which is itself regulated by the azasperpyranone transcriptional regulator ATEG_07667. {ECO:0000269|PubMed:31908094}. |
| Subcellular Location | |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 27,521 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |