E9F5E7 · SUBA_METRA
- ProteinNon-reducing polyketide synthase subA
- GenesubA
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids2181 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Non-reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of the immunosuppressants subglutinols, meroterpenoids consisting of an alpha-pyrone (4-hydroxy-5,6-dimethyl-2-pyrone) moiety attached to a decalin core fused to a five-membered cyclic ether carrying a prenylside chain (PubMed:27189118).
The first step of the pathway is the synthesis of the alpha-pyrone moiety by the polyketide synthase subA via condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units and 2 methylations (PubMed:27189118).
The alpha-pyrone is then combined with geranylgeranyl pyrophosphate (GGPP) formed by the GGPP synthase subD through the action of the prenyltransferase subC to yield a linear alpha-pyrone diterpenoid (PubMed:27189118).
Subsequent steps in the subglutinol biosynthetic pathway involve the decalin core formation, which is thought to be initiated by the epoxidation of the C10-C11 olefin by the FAD-dependent oxidoreductase subE (Probable). The following cyclization cascade would be catalyzed by the terpene cyclase subB (Probable). Lastly, the FAD-dependent dehydrogenase subF probably catalyzes the five-membered cyclic ether formation to complete the formation of subglutinol A (Probable). Subsequent redox reactions appear to give rise to subglutinol C and D, however, it remains unclear which enzymes are responsible for these transformations (Probable). SubD may have secondary function in the conversion of the identified subglutinols to subglutinol analog 45, which seems to be the major product of the cluster (PubMed:34863012).
The first step of the pathway is the synthesis of the alpha-pyrone moiety by the polyketide synthase subA via condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units and 2 methylations (PubMed:27189118).
The alpha-pyrone is then combined with geranylgeranyl pyrophosphate (GGPP) formed by the GGPP synthase subD through the action of the prenyltransferase subC to yield a linear alpha-pyrone diterpenoid (PubMed:27189118).
Subsequent steps in the subglutinol biosynthetic pathway involve the decalin core formation, which is thought to be initiated by the epoxidation of the C10-C11 olefin by the FAD-dependent oxidoreductase subE (Probable). The following cyclization cascade would be catalyzed by the terpene cyclase subB (Probable). Lastly, the FAD-dependent dehydrogenase subF probably catalyzes the five-membered cyclic ether formation to complete the formation of subglutinol A (Probable). Subsequent redox reactions appear to give rise to subglutinol C and D, however, it remains unclear which enzymes are responsible for these transformations (Probable). SubD may have secondary function in the conversion of the identified subglutinols to subglutinol analog 45, which seems to be the major product of the cluster (PubMed:34863012).
Pathway
Secondary metabolite biosynthesis; terpenoid biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 525 | For beta-ketoacyl synthase activity | ||||
Sequence: C | ||||||
Active site | 661 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 702 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 977 | For acyl/malonyl transferase activity | ||||
Sequence: S |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | 3-oxoacyl-[acyl-carrier-protein] synthase activity | |
Molecular Function | methyltransferase activity | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | methylation | |
Biological Process | secondary metabolite biosynthetic process | |
Biological Process | terpenoid biosynthetic process |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNon-reducing polyketide synthase subA
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Sordariomycetes > Hypocreomycetidae > Hypocreales > Clavicipitaceae > Metarhizium
Accessions
- Primary accessionE9F5E7
Proteomes
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000451337 | 1-2181 | Non-reducing polyketide synthase subA | |||
Sequence: MRVNTPSLLICGPMISQADAAYLPQVRSSLVHNKDLSYLREAVSELPNLWLRLVREEPSLGEIDVALFLDNLSQWVKGNSTQPTASRDSRNTQWAVLTVLVHIVEYMEYLDNFSSRDEDGCGHLDAHAALLDHLHDGGIQGLCIGLLTALALACAPSHAEIAKYGAVAVRLALCCGAYIDLNEAKSPAKTICVTTRWPGDDGDDKGDIDRKCDEQLQAILDTYPDAYKSVQTDVSTVTITTNEGDVLALLGELEKGGATSKRIDLHGRYHYGGNQAALLKLLQLSKALPMLQFPRGSRLVVPVRNNCSGSIVEDNTALHEMALRCILVENAEWLKTISSSISANTRQAQLLVLGPVNCVPRSLLLRSPQPISLSVSGKADNIYPDQSIAIIGSSCCFPGAENPRQLWEFIRTKQTHGVVDAAGSFDCSFFRKSPREAEYMDPQQRLGLHLAQEALESGGYFSPSSSATKNVGCYLGISSCDYEDNVNSHPPTAYSFTGTARAFASGRISHFFGLTGPSMVIDTACSSSGVAINTACRAIQSGECTMALAGGINLISREARTQENLAAASFLSPTGECRPFDSKANGYRRGEGGGLVLLKKLSSAVADGDVVLGVIAATAVNQSEGNKSITLPSSESQTSLYQRVLESANLKPRHISYVEAHGTGTQKGDPIECQSIRTVFGGTVRPACRQLHVGSIKSNIGHSEAASGIAALLKVLQMLHHRVIPPQANFEELNPAISPLHDDNIEISRHTKPWEERFRAALVNNYGASGTNAAMLVCQPPSIQHRLPLFPNRPCHYPILLTSHSNESLQLYCRNILRFIENQNNVVSDEEVLANTAFHLAQRQDHSLSFRLTFSVSSIEELKLKLQQQSTSQSYKDGPIQKHSAQPVVVVLAGQTGRRVRLSHEIYASSELLQRHLGRCDRALQTMGFASLFPGIFDTEPLEDLVQAHCMLFSLQYSVAMSWIDSGLKIDALVGHSLGQLTALCISGMLSLQDGLKLISGRASLIQSKWGAECGAMLSVDADAETVQNLADSLPAGYKVEIACYNSSQSHVVVGTKAAITAFEKAADLRGVSLRRLAISHGFHSEMIDCILPDYNKLVQGLVLHPPAIAIEPCSQSGHSWANATPEIIARQSREPVYFANAISRLEKRFGSCIWLEAGWGSAGVNMARRALTHGPTRSLSTHSFYPAALGEPDSVKALADTTINLWNAGIRVQFWLYHRSQTGSPAPLELPLHPFMKSEYLLPVVKHSKKAQSEKDGQPIIQEKATLVSLIGKTQNAGVQTVEYSINQNSEEYSVYVRGRTVFEHLLAPVSMYIESATRAFRLLSTHKLVSFSTSASMELKNLKLHAPFGFDLQKSLRMILRKLGEDAWEFRVESHPIHEKERGSVLQATGVITLQEVYSHLAPHRPLLRRLYDRCEELGKDVSASVVQGDFIKKIINSVARYDDRYIGVRSITSKGFETVAHVFEPEIASQFTPTTPFNPLLLDNFLLIAEIQANNLGGVTPDEIYVGNGFDAATAYTNAEDSEPSTKGHWVGLYSFDHQENDGILCDIFIFCAERKILSMTILGAKFQKIAISSLKRALKTINGVPQTSGGRTPSSSITEFISGDDASPCLPIPGADKPIFIREDDFGFMTTSGHMDEENHLIPEYDVISGSSRSTSSSPPSLESRSQAMDTEEITEGAGSALFNLLSNHLNYPKGLSPDTPLGALGLDSLVAIQLQSDIEQMFGKNSQLMDINESSTFSTLFHTIFPQQQTDQFGFVPLHDQTGKDRLESAVPLRLGYSHIKHAAPSFNDSLDRSNTLFIRQVPHAMDALKQNISSTIKAAGFHDFFSDVHPRQRSLVLAYIVHAFRELGCDIRSLEVGDELPSVQFKPKYQNVMNRLFDILGSEGVINVLNKRYLGGLASFPERSAEDMHKAIMNDYPSYHPDHKLLHTTGARLADCISGKVDPLQILFQNATSIKLLEDVYVKSPMFGTGNLLLGEFMNCLFSYNKTPDRLNHIRILEIGAGTGATTQLVVDRLLACNVDFTYTFTDVSAALVASAREKLTSRYGQHQRFDMEFETLNIEKEPPASFAQSYDLVISANCIHATRDLRKSCSNIEKLLRKDGGVLCLLELTRPLEWLDCVFGLLDGWWRFDDHRTYALAGEQDWKTILLQSGFGHVDWTDDGSREAQQLRLITAWR | ||||||
Modified residue | 1713 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S |
Keywords
- PTM
Expression
Induction
The subglutinol cluster is highly expressed when mycelia and hyphae are transferred to fresh media for a 3 hour induction period, remaining expressed under conditions of heat shock (PubMed:34863012).
The cluster is repressed in cultures reaching stationary phase or in early germinating cultures, as well as under conditions of UV, salt and oxidative stress (PubMed:34863012).
The cluster is repressed in cultures reaching stationary phase or in early germinating cultures, as well as under conditions of UV, salt and oxidative stress (PubMed:34863012).
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 74-180 | N-terminal acylcarrier protein transacylase domain (SAT) | ||||
Sequence: QWVKGNSTQPTASRDSRNTQWAVLTVLVHIVEYMEYLDNFSSRDEDGCGHLDAHAALLDHLHDGGIQGLCIGLLTALALACAPSHAEIAKYGAVAVRLALCCGAYID | ||||||
Domain | 347-779 | Ketosynthase family 3 (KS3) | ||||
Sequence: QAQLLVLGPVNCVPRSLLLRSPQPISLSVSGKADNIYPDQSIAIIGSSCCFPGAENPRQLWEFIRTKQTHGVVDAAGSFDCSFFRKSPREAEYMDPQQRLGLHLAQEALESGGYFSPSSSATKNVGCYLGISSCDYEDNVNSHPPTAYSFTGTARAFASGRISHFFGLTGPSMVIDTACSSSGVAINTACRAIQSGECTMALAGGINLISREARTQENLAAASFLSPTGECRPFDSKANGYRRGEGGGLVLLKKLSSAVADGDVVLGVIAATAVNQSEGNKSITLPSSESQTSLYQRVLESANLKPRHISYVEAHGTGTQKGDPIECQSIRTVFGGTVRPACRQLHVGSIKSNIGHSEAASGIAALLKVLQMLHHRVIPPQANFEELNPAISPLHDDNIEISRHTKPWEERFRAALVNNYGASGTNAAMLVCQ | ||||||
Region | 891-1193 | Malonyl-CoA:ACP transacylase (MAT) domain | ||||
Sequence: VLAGQTGRRVRLSHEIYASSELLQRHLGRCDRALQTMGFASLFPGIFDTEPLEDLVQAHCMLFSLQYSVAMSWIDSGLKIDALVGHSLGQLTALCISGMLSLQDGLKLISGRASLIQSKWGAECGAMLSVDADAETVQNLADSLPAGYKVEIACYNSSQSHVVVGTKAAITAFEKAADLRGVSLRRLAISHGFHSEMIDCILPDYNKLVQGLVLHPPAIAIEPCSQSGHSWANATPEIIARQSREPVYFANAISRLEKRFGSCIWLEAGWGSAGVNMARRALTHGPTRSLSTHSFYPAALGEP | ||||||
Region | 1269-1401 | N-terminal hotdog fold | ||||
Sequence: VSLIGKTQNAGVQTVEYSINQNSEEYSVYVRGRTVFEHLLAPVSMYIESATRAFRLLSTHKLVSFSTSASMELKNLKLHAPFGFDLQKSLRMILRKLGEDAWEFRVESHPIHEKERGSVLQATGVITLQEVYS | ||||||
Domain | 1269-1579 | PKS/mFAS DH | ||||
Sequence: VSLIGKTQNAGVQTVEYSINQNSEEYSVYVRGRTVFEHLLAPVSMYIESATRAFRLLSTHKLVSFSTSASMELKNLKLHAPFGFDLQKSLRMILRKLGEDAWEFRVESHPIHEKERGSVLQATGVITLQEVYSHLAPHRPLLRRLYDRCEELGKDVSASVVQGDFIKKIINSVARYDDRYIGVRSITSKGFETVAHVFEPEIASQFTPTTPFNPLLLDNFLLIAEIQANNLGGVTPDEIYVGNGFDAATAYTNAEDSEPSTKGHWVGLYSFDHQENDGILCDIFIFCAERKILSMTILGAKFQKIAISSLK | ||||||
Region | 1276-1573 | Product template (PT) domain | ||||
Sequence: QNAGVQTVEYSINQNSEEYSVYVRGRTVFEHLLAPVSMYIESATRAFRLLSTHKLVSFSTSASMELKNLKLHAPFGFDLQKSLRMILRKLGEDAWEFRVESHPIHEKERGSVLQATGVITLQEVYSHLAPHRPLLRRLYDRCEELGKDVSASVVQGDFIKKIINSVARYDDRYIGVRSITSKGFETVAHVFEPEIASQFTPTTPFNPLLLDNFLLIAEIQANNLGGVTPDEIYVGNGFDAATAYTNAEDSEPSTKGHWVGLYSFDHQENDGILCDIFIFCAERKILSMTILGAKFQKI | ||||||
Region | 1425-1579 | C-terminal hotdog fold | ||||
Sequence: SASVVQGDFIKKIINSVARYDDRYIGVRSITSKGFETVAHVFEPEIASQFTPTTPFNPLLLDNFLLIAEIQANNLGGVTPDEIYVGNGFDAATAYTNAEDSEPSTKGHWVGLYSFDHQENDGILCDIFIFCAERKILSMTILGAKFQKIAISSLK | ||||||
Region | 1652-1673 | Disordered | ||||
Sequence: ISGSSRSTSSSPPSLESRSQAM | ||||||
Domain | 1677-1753 | Carrier | ||||
Sequence: EITEGAGSALFNLLSNHLNYPKGLSPDTPLGALGLDSLVAIQLQSDIEQMFGKNSQLMDINESSTFSTLFHTIFPQQ | ||||||
Region | 1982-2164 | Methyltransferase (CMeT) domain | ||||
Sequence: EFMNCLFSYNKTPDRLNHIRILEIGAGTGATTQLVVDRLLACNVDFTYTFTDVSAALVASAREKLTSRYGQHQRFDMEFETLNIEKEPPASFAQSYDLVISANCIHATRDLRKSCSNIEKLLRKDGGVLCLLELTRPLEWLDCVFGLLDGWWRFDDHRTYALAGEQDWKTILLQSGFGHVDWT |
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; a methyltransferase (CMeT) domain responsible for methylations; 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
- Length2,181
- Mass (Da)239,620
- Last updated2011-04-05 v1
- Checksum89DBF2DC481E70DC
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
ADNJ02000014 EMBL· GenBank· DDBJ | EFY96950.1 EMBL· GenBank· DDBJ | Genomic DNA |