| IED ID | IndEnz0010000291 |
| Enzyme Type ID | esterase000291 |
| Protein Name |
Probable esterase azaC EC 3.1.2.- Azaphilone biosynthesis cluster protein azaC |
| Gene Name | azaC ASPNIDRAFT_50208 |
| Organism | Aspergillus niger (strain ATCC 1015 / CBS 113.46 / FGSC A1144 / LSHB Ac4 / NCTC 3858a / NRRL 328 / USDA 3528.7) |
| 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 niger Aspergillus niger (strain ATCC 1015 / CBS 113.46 / FGSC A1144 / LSHB Ac4 / NCTC 3858a / NRRL 328 / USDA 3528.7) |
| Enzyme Sequence | MPAKLPDDTTLRLPRILCLHGGGTNARIFRAQCRVLSTLLSPHFRLCFAEAPFPSQPGPDVVSVYRHFGDFKSWIPMPPNPSISPTNVAKKILNSLRHTIEEDDRSGADGEWVAVLGFSQGARLAASLLFQEQNGGSGMVGVYGGVNFRFAVLLAGRGPMIPLDMDAMASVSSAVLSLPTIHVHGLQDPGLEHHRELLERYCNRETASLIEWEGNHRVPIKMKDARVVVEEILKIAQKTGCLVPPTIQGGGTSNCGALLLDR |
| Enzyme Length | 262 |
| Uniprot Accession Number | G3XMB7 |
| Absorption | |
| Active Site | ACT_SITE 119; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P38777; ACT_SITE 188; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P38777; ACT_SITE 216; /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 gene cluster that mediates the biosynthesis of azaphilones, a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibiting a broad range of bioactivities (PubMed:22921072). In the first step, the non-reducing polyketide synthase azaA forms the hexaketide precursor from successive condensations of five malonyl-CoA units, presumably with a simple acetyl-CoA starter unit (PubMed:22921072). The reactive polyketide chain then undergoes a PT-mediated C2-C7 cyclization to afford the aromatic ring and is eventually released as an aldehyde through the R-domain (PubMed:22921072). The putative ketoreductase azaE is proposed to catalyze the reduction of the terminal ketone resulting in the early culture product FK17-P2a (PubMed:22921072). The monooxygenase azaH was demonstrated to be the only enzyme required to convert FK17-P2a to azanigerone E (PubMed:22921072). AzaH first hydroxylates the benzaldehyde intermediate FK17-P2a at C4, which triggers the formation of the pyran-ring to afford azanigerone E (PubMed:22921072). In parallel, the 2,4-dimethylhexanoyl chain is synthesized by the HR-PKS azaB and is proposed to be transferred to the C4-hydroxyl of azanigerone E by the acyltransferase azaD directly from the ACP domain of azaB (PubMed:22921072). Alternatively, the 2,4-dimethyl-hexanoyl chain may be offloaded from the HR-PKS as a carboxylic acid and converted to an acyl-CoA by azaF (PubMed:22921072). The resulting acyl-CoA molecule could then be taken up as a substrate by AzaD to form azanigerone B (PubMed:22921072). To yield the carboxylic acid substituent in azanigerone A, the hydroxypropyl side chain of azanigerone B would need to undergo a C-C oxidative cleavage catalyzed by cytochrome P450 AzaI (PubMed:22921072). AzaI is proposed to act on a vicinal diol that leads to a C-C bond scission either through an alkoxyradical intermediate or a peroxy complex (PubMed:22921072). In the biosynthesis of azanigerone A, azanigerone B first undergoes hydroxylation at C10, possibly catalyzed by one of the two FAD-dependent monooxygenases encoded in the cluster, azaG or azaL, resulting in the vicinal diol azanigerone C (PubMed:22921072). Oxidative cleavage of azanigerone C by azaI would yield the corresponding aldehyde derivative of azanigerone A (PubMed:22921072). Finally, the dehydrogenase azaJ is proposed to convert the aldehyde functional group into the carboxylic acid, completing the conversion from azanigerone B to azanigerone A (PubMed:22921072). Alternatively, the oxidation of aldehyde to carboxylic acid may be catalyzed by the same P450 enzyme azaI via consecutive oxidation or by endogenous alcohol dehydrogenase (PubMed:22921072). {ECO:0000269|PubMed:22921072}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Secondary metabolite biosynthesis. {ECO:0000269|PubMed:22921072}. |
| nucleotide Binding | |
| Features | Active site (3); Chain (1) |
| Keywords | Hydrolase;Reference proteome |
| Interact With | |
| Induction | INDUCTION: Expression is under the control of the azaphilone cluster-specific transcription factor azaR (PubMed:22921072). {ECO:0000269|PubMed:22921072}. |
| Subcellular Location | |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 28,477 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |