Q4WZB3 · AYG1_ASPFU
- ProteinHeptaketide hydrolyase ayg1
- Geneayg1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids406 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Heptaketide hydrolyase; part of the gene cluster that mediates the biosynthesis of dihydroxynaphthalene (DHN)-melanin, a bluish-green pigment and a structural component of the conidial wall (PubMed:10515939, PubMed:11350964, PubMed:15310761, PubMed:19156203).
The first step of the pathway is the production of the heptaketide naphtopyrone YWA1 by the polyketide synthase alb1 though condensation of acetyl-CoA with malonyl-CoA (PubMed:10515939).
The naphtopyrone YWA1 is then converted to the pentaketide 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) by the heptaketide hydrolyase ayp1 though chain-length shortening (PubMed:10515939, PubMed:11350964).
1,3,6,8-THN is substrate of the hydroxynaphthalene reductase arp2 to yield scytalone (PubMed:10515939, PubMed:11350964, PubMed:15310761).
The scytalone dehydratase arp1 then reduces scytalone to 1,3,8-THN (PubMed:10515939).
1,3,8-THN is also substrate of the hydroxynaphthalene reductase arp2 to yield vermelone (PubMed:10515939).
Vermelone is further converted by the multicopper oxidase abr1 to 1,8-DHN (PubMed:10515939).
Finally the laccase abr2 transforms 1,8-DHN to DHN-melanin (PubMed:10515939).
DHN-melanin biosynthesis appears to be initiated in endosomes where early enzymes (abl1, ayg1, arp1 and arp2) localize, with exocytosis leading to melanin deposition on the cell surface where late enzymes (abr1 and abr2) localize (PubMed:26972005).
DHN-melanin is an important structural component of the outer cell wall and is required for the presence of conidial surface hydrophobins (PubMed:19703288).
DHN-melanin also plays a crucial role in fungal virulence, including a protective role against the host's immune defenses (PubMed:19156203, PubMed:20145078, PubMed:21501368, PubMed:21573171, PubMed:21747802, PubMed:24818666).
DHN-melanin protects also conidia against amoeba predation (PubMed:25684622).
The first step of the pathway is the production of the heptaketide naphtopyrone YWA1 by the polyketide synthase alb1 though condensation of acetyl-CoA with malonyl-CoA (PubMed:10515939).
The naphtopyrone YWA1 is then converted to the pentaketide 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) by the heptaketide hydrolyase ayp1 though chain-length shortening (PubMed:10515939, PubMed:11350964).
1,3,6,8-THN is substrate of the hydroxynaphthalene reductase arp2 to yield scytalone (PubMed:10515939, PubMed:11350964, PubMed:15310761).
The scytalone dehydratase arp1 then reduces scytalone to 1,3,8-THN (PubMed:10515939).
1,3,8-THN is also substrate of the hydroxynaphthalene reductase arp2 to yield vermelone (PubMed:10515939).
Vermelone is further converted by the multicopper oxidase abr1 to 1,8-DHN (PubMed:10515939).
Finally the laccase abr2 transforms 1,8-DHN to DHN-melanin (PubMed:10515939).
DHN-melanin biosynthesis appears to be initiated in endosomes where early enzymes (abl1, ayg1, arp1 and arp2) localize, with exocytosis leading to melanin deposition on the cell surface where late enzymes (abr1 and abr2) localize (PubMed:26972005).
DHN-melanin is an important structural component of the outer cell wall and is required for the presence of conidial surface hydrophobins (PubMed:19703288).
DHN-melanin also plays a crucial role in fungal virulence, including a protective role against the host's immune defenses (PubMed:19156203, PubMed:20145078, PubMed:21501368, PubMed:21573171, PubMed:21747802, PubMed:24818666).
DHN-melanin protects also conidia against amoeba predation (PubMed:25684622).
Activity regulation
Serine protease inhibitors strongly inhibit activity (PubMed:15310761).
Moreover, 3,4-dichloroisocoumarinshows and 2-acetyl-1,3,6,8-tetrahydroxynaphthalene act also as a strong inhibitor (PubMed:15310761).
Moreover, 3,4-dichloroisocoumarinshows and 2-acetyl-1,3,6,8-tetrahydroxynaphthalene act also as a strong inhibitor (PubMed:15310761).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
44 μM | naphtopyrone YWA1 |
Pathway
Pigment biosynthesis; melanin biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 257 | Nucleophile | ||||
Sequence: S | ||||||
Active site | 352 | |||||
Sequence: D | ||||||
Active site | 380 | |||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endosome | |
Molecular Function | hydrolase activity | |
Biological Process | melanin biosynthetic process | |
Biological Process | pigment biosynthetic process | |
Biological Process | polyketide catabolic process |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameHeptaketide hydrolyase ayg1
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Fumigati
Accessions
- Primary accessionQ4WZB3
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Leads to a yellow-green color of conidia (PubMed:11350964, PubMed:26972005).
Impairs the accumulation of 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) (PubMed:11350964).
Results in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface (PubMed:24818666).
Decreases the protection against the host's immune defenses (PubMed:21501368).
Causes enhanced insect mortality compared to the parent strain in a wax moth Galleria mellonella infection model, probably through exacerbated immune response of the wax moth (PubMed:19156203).
Impairs the accumulation of 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) (PubMed:11350964).
Results in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface (PubMed:24818666).
Decreases the protection against the host's immune defenses (PubMed:21501368).
Causes enhanced insect mortality compared to the parent strain in a wax moth Galleria mellonella infection model, probably through exacerbated immune response of the wax moth (PubMed:19156203).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 257 | Results in a complete loss of enzyme activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 352 | Results in a complete loss of enzyme activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 380 | Results in a complete loss of enzyme activity. | ||||
Sequence: H → A |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000436878 | 1-406 | Heptaketide hydrolyase ayg1 | |||
Sequence: MPRWILGDKFDTVFPHKGSLKVLWESRWKSACSKSVYPFHDGSIEDFEPIFNHLISKNINDAASDEYTQAFLPTASALEEKAAQALQAGKHEEASNLLCRAAVVYRISRFPYVDITKPSSIKRVAFERQKQAYLKATSLWTQPIREVTVPHTYRTGNDGAHIPIYIRTPAGADQSNPVPIVLIMTGLDGYRSDNSQRTHEILARGWAAVVAEIPGTADCPADPADPASPDRLWDSVLSYLDQRPELNTAKMVVWGLSAGGYYAIRAAHTHRDRLLGAIAHGPGCHYYLDPEWLAKVNDHEYPFEITAAWATKHGYKTVEEFVAGAQKKFSLVETGIVDQPSCRLLLLNGVDDGVVPIEDCLVLFEHGSPKEGRFYKGLPHMGYPNSLPVSYEWLEQVLASPSKTKN |
Interaction
Structure
Sequence
- Sequence statusComplete
- Length406
- Mass (Da)45,217
- Last updated2005-07-05 v1
- ChecksumCA19A32372DC5B5B
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AAHF01000001 EMBL· GenBank· DDBJ | EAL94052.1 EMBL· GenBank· DDBJ | Genomic DNA |