A0A1L9WLF1 · AACUM_ASPA1
- ProteinAtrochrysone carboxyl ACP thioesterase AacuM
- GeneAacuM
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids312 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Atrochrysone carboxyl ACP thioesterase; part of the gene cluster that mediates the biosynthesis of the tetrahydroxanthone dimer secalonic acid D (PubMed:30996871, PubMed:33891392).
The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase AacuL (Probable). The atrochrysone carboxyl ACP thioesterase AacuM then breaks the thioester bond and releases the atrochrysone carboxylic acid from AacuL (Probable). Atrochrysone carboxylic acid is decarboxylated by the decarboxylase AacuI, and oxidized by the anthrone oxygenase AacuG to yield emodin (Probable). Emodin is then reduced to emodin hydroquinone by a yet unidentified oxidoreductase (Probable). A-ring reduction by the short chain dehydrogenase AacuN, dehydration by the scytalone dehydratase-like protein AacuK and probable spontaneous re-oxidation, results in overall deoxygenation to chrysophanol (PubMed:33891392).
Baeyer-Villiger oxidation by the Baeyer-Villiger monooxygenase (BVMO) AacuH then yields monodictyphenone (PubMed:33891392).
Monodictyphenone is transformed into compounds with the tetrahydroxanthone skeleton via methylesterification by the methyltransferase AacuQ, followed by the action of the flavin-dependent monooxygenase AacuC, the isomerase AacuP, and the short chain dehydrogenase/reductase AacuF or AacuD (PubMed:33891392).
AacuF and AacuD should accept the same compound as a substrate but perform the ketoreduction with a different stereoselectivity, thus yielding blennolides B and A, respectively (PubMed:33891392).
In the final step of the biosynthesis, the cytochrome P450 monooxygenase AacuE accepts blennolide B and/or blennolide A to conduct the dimerization reaction to furnish the tetrahydroxanthone dimers, secalonic acids D, B, and F (PubMed:33891392).
The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase AacuL (Probable). The atrochrysone carboxyl ACP thioesterase AacuM then breaks the thioester bond and releases the atrochrysone carboxylic acid from AacuL (Probable). Atrochrysone carboxylic acid is decarboxylated by the decarboxylase AacuI, and oxidized by the anthrone oxygenase AacuG to yield emodin (Probable). Emodin is then reduced to emodin hydroquinone by a yet unidentified oxidoreductase (Probable). A-ring reduction by the short chain dehydrogenase AacuN, dehydration by the scytalone dehydratase-like protein AacuK and probable spontaneous re-oxidation, results in overall deoxygenation to chrysophanol (PubMed:33891392).
Baeyer-Villiger oxidation by the Baeyer-Villiger monooxygenase (BVMO) AacuH then yields monodictyphenone (PubMed:33891392).
Monodictyphenone is transformed into compounds with the tetrahydroxanthone skeleton via methylesterification by the methyltransferase AacuQ, followed by the action of the flavin-dependent monooxygenase AacuC, the isomerase AacuP, and the short chain dehydrogenase/reductase AacuF or AacuD (PubMed:33891392).
AacuF and AacuD should accept the same compound as a substrate but perform the ketoreduction with a different stereoselectivity, thus yielding blennolides B and A, respectively (PubMed:33891392).
In the final step of the biosynthesis, the cytochrome P450 monooxygenase AacuE accepts blennolide B and/or blennolide A to conduct the dimerization reaction to furnish the tetrahydroxanthone dimers, secalonic acids D, B, and F (PubMed:33891392).
Catalytic activity
- atrochrysone carboxyl-[ACP] + H2O = atrochrysone carboxylate + H+ + holo-[ACP]This reaction proceeds in the forward direction.
Cofactor
Note: Binds 2 Zn2+ ions per subunit.
Biotechnology
Secalonic acids show unprecedented anticancer activities against various human cancer cells and might be interesting for further derivatization, targeting diseases such as cancer.
Pathway
Secondary metabolite biosynthesis.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 103 | Zn2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 105 | Zn2+ 1 (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Active site | 107 | Proton donor/acceptor | ||||
Sequence: D | ||||||
Binding site | 107 | Zn2+ 2 (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 108 | Zn2+ 2 (UniProtKB | ChEBI); catalytic | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | hydrolase activity | |
Molecular Function | metal ion binding | |
Biological Process | secondary metabolite biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAtrochrysone carboxyl ACP thioesterase AacuM
- EC number
- Short namesACTE AacuM
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Circumdati
Accessions
- Primary accessionA0A1L9WLF1
Proteomes
Organism-specific databases
Phenotypes & Variants
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000453431 | 1-312 | Atrochrysone carboxyl ACP thioesterase AacuM | |||
Sequence: MGEGGYRQINKTLNVCAFDDYLVTQQSRLPKLLDIEQLSPRVLRVLGQNAGKFTLQGTNTYIVGTGQHRLIIDTAQGYREWADLIDVTLSNRSISLSHVFLTHWHGDHTGGVPDLIRMYPHLADGIYKNSPEQGQHPIEEGQIFKVEGATIRAVHGPGHSHDHMCFVLEEENAMFTGDNVLGHGTSAVEQLGLYMDTLRKLQAQGCRTGYPAHGAVIPDLNLKIATELAQKTRREKQCLAALGRIRKERPTGQLASVTVGELIDVVHGTRVNEEVRKMALEPFMEEVLRKLAEDGKVAFRVRKGVKTWFALT |
Interaction
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length312
- Mass (Da)34,766
- Last updated2017-03-15 v1
- Checksum13A86B161887CD50
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
KV878984 EMBL· GenBank· DDBJ | OJJ96971.1 EMBL· GenBank· DDBJ | Genomic DNA |