A0A1L9WN37 · ACUA_ASPA1
- Protein6-methylsalicylic acid synthase acuA
- GeneacuA
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1749 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
6-methylsalicylic acid synthase; part of the gene cluster that mediates the biosynthesis of aculins (PubMed:26374386).
The pathway begins with the synthesis of 6-methylsalicylic acid by the polyketide synthase (PKS) acuA via condensation of acetate and malonate units (PubMed:26374386).
The 6-methylsalicylic acid decarboxylase acuB then catalyzes the decarboxylation of 6-methylsalicylic acid to yield m-cresol (also known as 3-methylphenol) (Probable). These first reactions occur in the cytosol (By similarity).
The intermediate m-cresol is then transported into the endoplasmic reticulum where the cytochrome P450 monooxygenase acuC converts it to m-hydroxybenzyl alcohol, which is further converted to gentisyl alcohol by the cytochrome P450 monooxygenase acuD (Probable). Gentisyl alcohol is further oxidized by the oxidoreductase acuE that probably catalyzes hydroxylation of the aromatic ring (Probable). The aromatic system might then be opened by oxidation through a Baeyer-Villiger type of oxidation, which could be catalyzed by acuF, with the carboxylic acid at C-1 subsequently reduced to an aldehyde by acuG (Probable). Subsequently, a hemiacetal is formed, before the dehydrogenase acuH would reduce the double bond between C-4 and C-6 (Probable). Finally, keto-enol tautomerism results in formation of aculinic acid, which exists as two diastereomers (both R/S configurations at C-1) by non-enzymatic hemiacetal formation (Probable). The carboxypeptidase acuI could be involved in the linking of aculinic acid to an aculene A moiety produced by the aculene biosynthesis cluster and which leads to the production of aculin A (Probable). AcuI may also be involved in the attachment of proline to aculinic acid to form epi-aculins A and B (Probable)
The pathway begins with the synthesis of 6-methylsalicylic acid by the polyketide synthase (PKS) acuA via condensation of acetate and malonate units (PubMed:26374386).
The 6-methylsalicylic acid decarboxylase acuB then catalyzes the decarboxylation of 6-methylsalicylic acid to yield m-cresol (also known as 3-methylphenol) (Probable). These first reactions occur in the cytosol (By similarity).
The intermediate m-cresol is then transported into the endoplasmic reticulum where the cytochrome P450 monooxygenase acuC converts it to m-hydroxybenzyl alcohol, which is further converted to gentisyl alcohol by the cytochrome P450 monooxygenase acuD (Probable). Gentisyl alcohol is further oxidized by the oxidoreductase acuE that probably catalyzes hydroxylation of the aromatic ring (Probable). The aromatic system might then be opened by oxidation through a Baeyer-Villiger type of oxidation, which could be catalyzed by acuF, with the carboxylic acid at C-1 subsequently reduced to an aldehyde by acuG (Probable). Subsequently, a hemiacetal is formed, before the dehydrogenase acuH would reduce the double bond between C-4 and C-6 (Probable). Finally, keto-enol tautomerism results in formation of aculinic acid, which exists as two diastereomers (both R/S configurations at C-1) by non-enzymatic hemiacetal formation (Probable). The carboxypeptidase acuI could be involved in the linking of aculinic acid to an aculene A moiety produced by the aculene biosynthesis cluster and which leads to the production of aculin A (Probable). AcuI may also be involved in the attachment of proline to aculinic acid to form epi-aculins A and B (Probable)
Catalytic activity
- 3 malonyl-CoA + acetyl-CoA + NADPH + 3 H+ = 6-methylsalicylate + 3 CO2 + NADP+ + 4 CoA + H2OThis reaction proceeds in the forward direction.
Pathway
Secondary metabolite biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 165 | For beta-ketoacyl synthase activity | ||||
Sequence: C | ||||||
Active site | 300 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 340 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 920 | Proton acceptor; for dehydratase activity | ||||
Sequence: H | ||||||
Active site | 1085 | Proton donor; for dehydratase activity | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | 3-oxoacyl-[acyl-carrier-protein] synthase activity | |
Molecular Function | 6-methylsalicylic acid synthase activity | |
Molecular Function | fatty acid synthase activity | |
Molecular Function | phosphopantetheine binding | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | secondary metabolite biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name6-methylsalicylic acid synthase acuA
- EC number
- Short names6MSAS
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Circumdati
Accessions
- Primary accessionA0A1L9WN37
Proteomes
Organism-specific databases
Subcellular Location
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000450412 | 1-1749 | 6-methylsalicylic acid synthase acuA | |||
Sequence: MACRVAGNNNNPEQLWQSLLQKKDASGEIPEMRWEPYLRRDSRNAKILKETTSRGYFLDRLEDFDGQFFGISPKEAEQMDPQQRLSLEVTWEALENAGITARSLSGSDTAVFWGVNSDDYSKLVLEDLPNVEAWMGIGTAYCGVPNRISYHLNLMGPSTAVDAACASSLVAVHHGVQAIILGESKVAIVGGVNALCGPGLTRVLDKAGAVSSEGRCCSFDNDVKGYGRGEGAAAIVLKNLSAAIKDGDHIMAVIKGTAVAQDGKTNGIMAPNAKAQQLVAHNALKVGNIDPLTVGYVEAHATSTPLGDPTEVSAIAAVYGADREPEAPCFIGSIKPNIGHLEAGAGAMGFIKAVMAVQKGVLAPQANLTTLTKKIDWDNVGLKVVQQETKWPATDDVRRAAICSYGYGGTVSHAVIEQFNFPETLDLKPGASATNPTVLLLSGPQEKRLPIQARALRNWLQADGSQQDLQRVAATLAVRRDHHDYRAAIVVESKEDAIQALGHLADGANDAWTSQSRVFGSGINRDVVWVFSGHGAQWADMGKELLQNPIFYQAVQPLDEIVEAEIGLSPIALLRSGEFEASDHVQILTYIMQIGISAVLHSHGVYPQAIIGHSVGEIAASVVAGALTAEEGAVLITRRSVLYRQVMGQGGMILVNKPYAEVAQELAGREDLVVAIDSSPSSCVVAGSTEAVAEKAAEFKERSIKTFTVRTDIAFHSPMLNQLVDPLMQSLEGSLAPTTPTRAKLYSTSLRDPRGSDLRDATYWANNMVNPVHLTSAVQAALDDSYRVFLEVSSHPLVSHSINETIMDAGIEDYCMIPTLARKKPSEKSILHAVGQLHTRGANVDWKSQLSGPWAGGLPNTSWMHKPTWRQIGAGPVSTSQTHDVEKHTLLGQRIGVAGTDTVVYTTRLDNESKPFPGSHPLHGTEIVPAAGLVNTFVKATGATVLNNVVLRVPVAINAPRSVQIVAQREDVKIMSRLIQENEGNNDDSSWVTHTTARWESSSSSPVPAQIDVEATKARIGTRLRDEFSIDYLDKVGVSAMGFPWAVTEHYGNTKEMIARVDAAPSVAADAELPWDASSWAPILDAATSVGSTIFFNEPRLRMPAQIERVDIFTRANPPKVGWLYVQEASDTALASHVSVCDEAGNVVAKFTSMRFSEIEGTPGVSGSMESLVHQMAWPPAVPAEEPLPINKLLLISQDVPLREAYAATISSSTQVTLLANANDLIINRAESLLTKETAIVYIPSQVSSLQDVPKSAETFTWQLLELIKFVVNNALPVKIFVVTSNTGEGETPTALAHAPLVGLSRVIASEHPDQFGGLIDTEVLTFPLTTMRYIQGADIIRIRDGVARTMRLRSLPRHRLIQQQDQQQQQPQLLPRPDGTYLITGGLGALGLEVADFLVTQGARRVILISRRGLPPRRLWSKMEPSSPLAPTITKILDLEARGATIHVLPLDISQLTAADALTTALDTLSLPPVRGVVHAAGVLDNELVLDTTPDAFARVLAPKITGGLVLNEVFPPQSVDFFILFSSCGQLVGFTGQSSYGAGNSFLDALASHRQARGDRGARAFQWTAWRALGMGASTDFINAELASKGITDVTADEAFAAWRHAARYEGIDHAVVLRALPLDADEPLPSPALADIIVRRSASASADSSPSSSPEKQTIPTSGPELKAYLDKAIRGCVAAVLHLPAADEVDSKAALADLGVDSVMTVTLRQKLQQALRVKVPPTLTWSHPTVGHLVGWFAEKVGKE | ||||||
Modified residue | 1706 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S |
Keywords
- PTM
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-418 | Ketosynthase family 3 (KS3) | ||||
Sequence: MACRVAGNNNNPEQLWQSLLQKKDASGEIPEMRWEPYLRRDSRNAKILKETTSRGYFLDRLEDFDGQFFGISPKEAEQMDPQQRLSLEVTWEALENAGITARSLSGSDTAVFWGVNSDDYSKLVLEDLPNVEAWMGIGTAYCGVPNRISYHLNLMGPSTAVDAACASSLVAVHHGVQAIILGESKVAIVGGVNALCGPGLTRVLDKAGAVSSEGRCCSFDNDVKGYGRGEGAAAIVLKNLSAAIKDGDHIMAVIKGTAVAQDGKTNGIMAPNAKAQQLVAHNALKVGNIDPLTVGYVEAHATSTPLGDPTEVSAIAAVYGADREPEAPCFIGSIKPNIGHLEAGAGAMGFIKAVMAVQKGVLAPQANLTTLTKKIDWDNVGLKVVQQETKWPATDDVRRAAICSYGYGGTVSHAVIEQ | ||||||
Region | 528-843 | Malonyl-CoA:ACP transacylase (MAT) domain | ||||
Sequence: VWVFSGHGAQWADMGKELLQNPIFYQAVQPLDEIVEAEIGLSPIALLRSGEFEASDHVQILTYIMQIGISAVLHSHGVYPQAIIGHSVGEIAASVVAGALTAEEGAVLITRRSVLYRQVMGQGGMILVNKPYAEVAQELAGREDLVVAIDSSPSSCVVAGSTEAVAEKAAEFKERSIKTFTVRTDIAFHSPMLNQLVDPLMQSLEGSLAPTTPTRAKLYSTSLRDPRGSDLRDATYWANNMVNPVHLTSAVQAALDDSYRVFLEVSSHPLVSHSINETIMDAGIEDYCMIPTLARKKPSEKSILHAVGQLHTRGAN | ||||||
Region | 888-1006 | N-terminal hotdog fold | ||||
Sequence: HTLLGQRIGVAGTDTVVYTTRLDNESKPFPGSHPLHGTEIVPAAGLVNTFVKATGATVLNNVVLRVPVAINAPRSVQIVAQREDVKIMSRLIQENEGNNDDSSWVTHTTARWESSSSSP | ||||||
Region | 888-1160 | Dehydratase (DH) domain | ||||
Sequence: HTLLGQRIGVAGTDTVVYTTRLDNESKPFPGSHPLHGTEIVPAAGLVNTFVKATGATVLNNVVLRVPVAINAPRSVQIVAQREDVKIMSRLIQENEGNNDDSSWVTHTTARWESSSSSPVPAQIDVEATKARIGTRLRDEFSIDYLDKVGVSAMGFPWAVTEHYGNTKEMIARVDAAPSVAADAELPWDASSWAPILDAATSVGSTIFFNEPRLRMPAQIERVDIFTRANPPKVGWLYVQEASDTALASHVSVCDEAGNVVAKFTSMRFSEIE | ||||||
Domain | 888-1165 | PKS/mFAS DH | ||||
Sequence: HTLLGQRIGVAGTDTVVYTTRLDNESKPFPGSHPLHGTEIVPAAGLVNTFVKATGATVLNNVVLRVPVAINAPRSVQIVAQREDVKIMSRLIQENEGNNDDSSWVTHTTARWESSSSSPVPAQIDVEATKARIGTRLRDEFSIDYLDKVGVSAMGFPWAVTEHYGNTKEMIARVDAAPSVAADAELPWDASSWAPILDAATSVGSTIFFNEPRLRMPAQIERVDIFTRANPPKVGWLYVQEASDTALASHVSVCDEAGNVVAKFTSMRFSEIEGTPGV | ||||||
Region | 1021-1165 | C-terminal hotdog fold | ||||
Sequence: GTRLRDEFSIDYLDKVGVSAMGFPWAVTEHYGNTKEMIARVDAAPSVAADAELPWDASSWAPILDAATSVGSTIFFNEPRLRMPAQIERVDIFTRANPPKVGWLYVQEASDTALASHVSVCDEAGNVVAKFTSMRFSEIEGTPGV | ||||||
Region | 1169-1629 | Product template (PT) domain | ||||
Sequence: MESLVHQMAWPPAVPAEEPLPINKLLLISQDVPLREAYAATISSSTQVTLLANANDLIINRAESLLTKETAIVYIPSQVSSLQDVPKSAETFTWQLLELIKFVVNNALPVKIFVVTSNTGEGETPTALAHAPLVGLSRVIASEHPDQFGGLIDTEVLTFPLTTMRYIQGADIIRIRDGVARTMRLRSLPRHRLIQQQDQQQQQPQLLPRPDGTYLITGGLGALGLEVADFLVTQGARRVILISRRGLPPRRLWSKMEPSSPLAPTITKILDLEARGATIHVLPLDISQLTAADALTTALDTLSLPPVRGVVHAAGVLDNELVLDTTPDAFARVLAPKITGGLVLNEVFPPQSVDFFILFSSCGQLVGFTGQSSYGAGNSFLDALASHRQARGDRGARAFQWTAWRALGMGASTDFINAELASKGITDVTADEAFAAWRHAARYEGIDHAVVLRALPLDADE | ||||||
Domain | 1671-1746 | Carrier | ||||
Sequence: AYLDKAIRGCVAAVLHLPAADEVDSKAALADLGVDSVMTVTLRQKLQQALRVKVPPTLTWSHPTVGHLVGWFAEKV |
Domain
Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,749
- Mass (Da)187,960
- Last updated2017-03-15 v1
- ChecksumE8001C481487766A
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
KV878982 EMBL· GenBank· DDBJ | OJJ97578.1 EMBL· GenBank· DDBJ | Genomic DNA |