D4AU31 · SWNK_ARTBC
- ProteinPKS-NRPS hybrid synthetase swnK
- GeneswnK
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids2567 (go to sequence)
- Protein existenceInferred from homology
- Annotation score4/5
Function
function
PKS-NRPS hybrid synthetase; part of the gene cluster that mediates the biosynthesis of swainsonine (SW), a cytotoxic fungal alkaloid and a potential cancer therapy drug (PubMed:28381497).
Swainsonine production occurs via a multibranched pathway and is dispensable for fungal colonization of plants and infection of insect hosts (By similarity).
The first step of swainsonine biosynthesis is the production of the precursor pipecolic acid (PA) via conversion of L-lysine (Lys) to 1-piperideine-6-carboxylate (P6C) by the aminotransferase swnA, the latter being further reduced to PA by the reductase swnR (By similarity).
The PKS-NRPS hybrid synthetase swnK uptakes and condensates PA and malonyl-CoA with and without skipping of the ketoreductase (KR) domain in order to produce 3 intermediates, 1-oxoindolizidine, (1S)-1-hydroxyindolizin, and (1R)-1-hydroxyindolizine; with the transisomer (1S)-1-hydroxyindolizin being predominant (By similarity).
The terminal thioester reductase (TE) domain of swnK is involved in reduction of the thioester bond to release the intermediate aldehydes (By similarity).
The oxidoreductase swnN could contribute to the reduction of 1-oxoindolizidine to (1S)-1-hydroxyindolizin and (1R)-1-hydroxyindolizine, contributing to the major route of SW production (By similarity).
The dioxygenase swnH2 would be responsible for the oxidization of (1R)-1-hydroxyindolizine into (1R,2S)-1,2-dihydroxyindolizine and of (1S)-1-hydroxyindolizin to yield both (1R,2S)-1,2-dihydroxyindolizine and (1S,2S)-1,2-dihydroxyindolizine (By similarity).
The dioxygenase swnH1 then performs the conversion of the 1,2-dihydroxyindolizine epimers to SW (By similarity).
Swainsonine production occurs via a multibranched pathway and is dispensable for fungal colonization of plants and infection of insect hosts (By similarity).
The first step of swainsonine biosynthesis is the production of the precursor pipecolic acid (PA) via conversion of L-lysine (Lys) to 1-piperideine-6-carboxylate (P6C) by the aminotransferase swnA, the latter being further reduced to PA by the reductase swnR (By similarity).
The PKS-NRPS hybrid synthetase swnK uptakes and condensates PA and malonyl-CoA with and without skipping of the ketoreductase (KR) domain in order to produce 3 intermediates, 1-oxoindolizidine, (1S)-1-hydroxyindolizin, and (1R)-1-hydroxyindolizine; with the transisomer (1S)-1-hydroxyindolizin being predominant (By similarity).
The terminal thioester reductase (TE) domain of swnK is involved in reduction of the thioester bond to release the intermediate aldehydes (By similarity).
The oxidoreductase swnN could contribute to the reduction of 1-oxoindolizidine to (1S)-1-hydroxyindolizin and (1R)-1-hydroxyindolizine, contributing to the major route of SW production (By similarity).
The dioxygenase swnH2 would be responsible for the oxidization of (1R)-1-hydroxyindolizine into (1R,2S)-1,2-dihydroxyindolizine and of (1S)-1-hydroxyindolizin to yield both (1R,2S)-1,2-dihydroxyindolizine and (1S,2S)-1,2-dihydroxyindolizine (By similarity).
The dioxygenase swnH1 then performs the conversion of the 1,2-dihydroxyindolizine epimers to SW (By similarity).
Catalytic activity
- 4 H+ + L-pipecolate + malonyl-CoA + 2 NADPH = (8aS)-octahydroindolizin-1-one + CO2 + CoA + 2 H2O + 2 NADP+This reaction proceeds in the forward direction.
- 5 H+ + L-pipecolate + malonyl-CoA + 3 NADPH = (1R,8aS)-octahydroindolizin-1-ol + CO2 + CoA + 2 H2O + 3 NADP+This reaction proceeds in the forward direction.
- 5 H+ + L-pipecolate + malonyl-CoA + 3 NADPH = (1S,8aS)-octahydroindolizin-1-ol + CO2 + CoA + 2 H2O + 3 NADP+This reaction proceeds in the forward direction.
Pathway
Mycotoxin biosynthesis.
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 793 | For beta-ketoacyl synthase activity | ||||
Sequence: C | ||||||
Active site | 928 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 968 | For beta-ketoacyl synthase activity | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | plasma membrane | |
Molecular Function | fatty acid synthase activity | |
Molecular Function | ligase activity | |
Molecular Function | methyltransferase activity | |
Molecular Function | oxidoreductase activity | |
Molecular Function | phosphopantetheine binding | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | methylation | |
Biological Process | secondary metabolite biosynthetic process |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePKS-NRPS hybrid synthetase swnK
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Onygenales > Arthrodermataceae > Trichophyton
Accessions
- Primary accessionD4AU31
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000441178 | 1-2567 | PKS-NRPS hybrid synthetase swnK | |||
Sequence: MLNHERTSSLSDQDYQSLVYDFNAAEDVSLLGGRLDQLFEKIVDTFPKNTALIHRDTEITFSELNESANILARSLIKRGLKHGDLVGLAVSRSIDLIVVVLAVLKLGAAYVPIDPLFPAERINQMVSDAGPKLILLSGSPSKGLASWKDICISVDEARDSSIVDTTNLEADIQPHDLSYVIYTSGSTGKPKGVEISHGAAANFLSSLRKYEPGCNEHDILLAITTISFDMSALELLLPLVSGTTMVIADTTAVKNPRELLELMRRHHVTILQATPATWTMLLESGWKGDPRLSKIICGGEPLTRQLADRLLAAADSVWNVYGPSETTYGSVGRVGEGDIVVGKPVVNGRIYVLDDNLSPAPVGCEGEIYIGGGSVSNGYRNNAELTRARFLANPFHGGLFFRTGDLGRFLAPGKLQVVGRIDGVVKIRGHRIDVGDIEAVLLDHASVSAAVVISHDDRLVAYCVLDGALSSDVSLDTILRPWVAERLPAYMLPAFFVQMDALPLSPNEKVNRKALPNPLEAIQSQASKQPTSELEQQLLAIWADILGHDRFGIEDNFFNLGGDSVRIIRMQTILERLLHRPIPTPKLFEHYTIKALAAYLTGIGMESTSNQELNTANDRFIGSHEDIAIVSMACRLPGGVTTPEEFWQLLQNGGDTIIDVPKDRWDAAKLYNSNPDIEGTSYCARGGFLDSVYSYDASFFGISPREAQAMDPAQNLMLELGWESFERAGYTKERLRGSATGVFIGVSNNGTTNSTPPDLKGYSITGSASAAMSGRLSYTLGLEGPSLVVDTACSSSLVATHLACNALRQGECNMALVGGVSLLLTPGIHVEFSKLRGLSADGRCRAFSQDTDGTGFSEGATSIVLKRLSDARRDGDTIHAVLRGTAVMHGGYSAGLTVPNSPGQVKLIRSALAQGAMKPCDIDYIEAHGTATKLGDPIEATALAEVFGNGRASSDPLRLGSAKSNVGHTQAAAGLVGLLKVVLSMRYNIIPKTLHVNEPTRSVDWKGANMELVLAPQPWPPRDHRLRRAGISAFGIGGTNAHIVVEEPPKLLARKNGCTLPTLVPSAIPFLLSGGSESALKAQAEKLRLHIESGIGKDDRLIDIAFSLATTRTHLQRRQVVVSRDKAQMLDALASVSSSSDKLFNVNEVGKPKIGMLFTGQGSQRLGMGKELYSVYPVFQTSIDNIAALFTQLDIPLLNVMWAEPESTHASLLNRTDYTQAALFALEVSLWNLWQSWGVQPDFLLGHSVGEIAAAHVSGILNLSDACRLVAMRGSLMQSLPSQGKMASVEASSIEVEEVVNELSKREEVEIAGYNTPSQTVISGNSEAVEAVTAHIARMGRKTKLLDTSHAFHSAHMNGMMDAFRAVTQDLQFETAKIPIISSMTGSLAAAGEPQCAEYWVQQARRAVRFSDAFQELIKQGANVFLEIGPSSTLCGLGAACVSDISQMSKALWLPSLKPRADEVSVVQNSAHELHMRHVPINWAEYFKPFDCERVSLPTYAFQRVSYQPTTKASWLNGLTQRNDSRTVVSGVENKMFEINWRQLSVDETLPRGIWGLFNLSNATTWVIAAHQALESSGVQLVQIAKLQDAMQLDGVLVFWDSDADVVQKAHAFSTAALAHLQEASNIGFAAPIVWVTRRAVGAGVGDQPVGLGAGPLWGLMRTTRSEHPELHLRLVDVDDETSLAALGTALAADSQTEISIRKGQLLVPHLERTNLASAPAGKPLLRTDGAVLVTGGLGDLGKRVSHRLVSCHGVRDLVLLSRTGKVSARADAFIVELSKLGANVTIVRCDVSELDSLKLVMQKFTADRPLRGVIHAAGVVDSGVLSSLTPEKCATTFAPKVDGLWNLHQLTKDMDLDIFMMFSSISGIMGLPGLGNYAAANSFIDTLSYLRRSQGLPATSVAYGVWGGDGMATTLVSTTRNHLSQLGLGYLEPEDGLKLFEQGVQCGKPLTIAAVLDLERLKSYYGEQGGIPPLLRSILGEQNDKLAVNTDMSLRDLLSNAAPAQHGRIVLHIVRKAIGKALGYAQMDEIDPSQPLKELGIDSLTAILVRNHLATLTGMTLPPNVALLRPNLKSLSEFILSLLQDSTDIGSTFSPKAKGVSRSNGTPKTNTTNGTSTNGTSTNGTSTNGTSTNGTHGTNGTPGSNGVSHTNGISKSNAEAKSNGGMKANGSAPKSVPHVDMAAIKRGVLDRSFQFENITKYPLSCLNTPKAVFVTGPTGFVGAFMVHELLKRGIAVYCLIRSSNLDQAQERMTQTLREYGLWKPEYASLIHSIIGDLSQPLLGLHEDMFDELADVVDAIIHSGALVDWMRPLEDYIGPNILGTHEILRLASHGRGKAVHFVSTISTLPIHLGYGLTELDGEYGYGTSKYLAERMIVAARFRGAVASSYRLPFVAASGTNGRFRLDRGDFLNNLVMGSLDLGAFPSLNTTLSSVLPVDYLCSTIAMIMTEDQGRIGEDYDFVNPRAPTFDTFFGIMGAASGNLEVLPFSQWHRRALEYAALNPKSPLARITTVLDGYTDETAGDLLKGSPVGKHVFGLDVYPAPLVGEDYIHKYLDSINSTRQNGGL | ||||||
Modified residue | 564 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S | ||||||
Modified residue | 2044 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S |
Keywords
- PTM
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 39-428 | Adenylation (A) domain | ||||
Sequence: FEKIVDTFPKNTALIHRDTEITFSELNESANILARSLIKRGLKHGDLVGLAVSRSIDLIVVVLAVLKLGAAYVPIDPLFPAERINQMVSDAGPKLILLSGSPSKGLASWKDICISVDEARDSSIVDTTNLEADIQPHDLSYVIYTSGSTGKPKGVEISHGAAANFLSSLRKYEPGCNEHDILLAITTISFDMSALELLLPLVSGTTMVIADTTAVKNPRELLELMRRHHVTILQATPATWTMLLESGWKGDPRLSKIICGGEPLTRQLADRLLAAADSVWNVYGPSETTYGSVGRVGEGDIVVGKPVVNGRIYVLDDNLSPAPVGCEGEIYIGGGSVSNGYRNNAELTRARFLANPFHGGLFFRTGDLGRFLAPGKLQVVGRIDGVVKIR | ||||||
Domain | 529-604 | Carrier 1 | ||||
Sequence: QPTSELEQQLLAIWADILGHDRFGIEDNFFNLGGDSVRIIRMQTILERLLHRPIPTPKLFEHYTIKALAAYLTGIG | ||||||
Domain | 624-1047 | Ketosynthase family 3 (KS3) | ||||
Sequence: HEDIAIVSMACRLPGGVTTPEEFWQLLQNGGDTIIDVPKDRWDAAKLYNSNPDIEGTSYCARGGFLDSVYSYDASFFGISPREAQAMDPAQNLMLELGWESFERAGYTKERLRGSATGVFIGVSNNGTTNSTPPDLKGYSITGSASAAMSGRLSYTLGLEGPSLVVDTACSSSLVATHLACNALRQGECNMALVGGVSLLLTPGIHVEFSKLRGLSADGRCRAFSQDTDGTGFSEGATSIVLKRLSDARRDGDTIHAVLRGTAVMHGGYSAGLTVPNSPGQVKLIRSALAQGAMKPCDIDYIEAHGTATKLGDPIEATALAEVFGNGRASSDPLRLGSAKSNVGHTQAAAGLVGLLKVVLSMRYNIIPKTLHVNEPTRSVDWKGANMELVLAPQPWPPRDHRLRRAGISAFGIGGTNAHIVVEE | ||||||
Region | 1157-1478 | Malonyl-CoA:ACP transacylase (MAT) domain | ||||
Sequence: LFTGQGSQRLGMGKELYSVYPVFQTSIDNIAALFTQLDIPLLNVMWAEPESTHASLLNRTDYTQAALFALEVSLWNLWQSWGVQPDFLLGHSVGEIAAAHVSGILNLSDACRLVAMRGSLMQSLPSQGKMASVEASSIEVEEVVNELSKREEVEIAGYNTPSQTVISGNSEAVEAVTAHIARMGRKTKLLDTSHAFHSAHMNGMMDAFRAVTQDLQFETAKIPIISSMTGSLAAAGEPQCAEYWVQQARRAVRFSDAFQELIKQGANVFLEIGPSSTLCGLGAACVSDISQMSKALWLPSLKPRADEVSVVQNSAHELHMRH | ||||||
Region | 1730-1908 | Ketoreductase (KR) domain | ||||
Sequence: GAVLVTGGLGDLGKRVSHRLVSCHGVRDLVLLSRTGKVSARADAFIVELSKLGANVTIVRCDVSELDSLKLVMQKFTADRPLRGVIHAAGVVDSGVLSSLTPEKCATTFAPKVDGLWNLHQLTKDMDLDIFMMFSSISGIMGLPGLGNYAAANSFIDTLSYLRRSQGLPATSVAYGVWG | ||||||
Domain | 2009-2084 | Carrier 2 | ||||
Sequence: RIVLHIVRKAIGKALGYAQMDEIDPSQPLKELGIDSLTAILVRNHLATLTGMTLPPNVALLRPNLKSLSEFILSLL | ||||||
Compositional bias | 2092-2165 | Polar residues | ||||
Sequence: STFSPKAKGVSRSNGTPKTNTTNGTSTNGTSTNGTSTNGTSTNGTHGTNGTPGSNGVSHTNGISKSNAEAKSNG | ||||||
Region | 2092-2176 | Disordered | ||||
Sequence: STFSPKAKGVSRSNGTPKTNTTNGTSTNGTSTNGTSTNGTSTNGTHGTNGTPGSNGVSHTNGISKSNAEAKSNGGMKANGSAPKS | ||||||
Region | 2213-2519 | Thioester reductase (TE) domain | ||||
Sequence: VFVTGPTGFVGAFMVHELLKRGIAVYCLIRSSNLDQAQERMTQTLREYGLWKPEYASLIHSIIGDLSQPLLGLHEDMFDELADVVDAIIHSGALVDWMRPLEDYIGPNILGTHEILRLASHGRGKAVHFVSTISTLPIHLGYGLTELDGEYGYGTSKYLAERMIVAARFRGAVASSYRLPFVAASGTNGRFRLDRGDFLNNLVMGSLDLGAFPSLNTTLSSVLPVDYLCSTIAMIMTEDQGRIGEDYDFVNPRAPTFDTFFGIMGAASGNLEVLPFSQWHRRALEYAALNPKSPLARITTVLDGYTD |
Domain
The architecture of swnK is the following one: adenylation (A), phosphopantetheine-binding/thiolation (T), beta-ketoacyl synthase (KS), malonyl-CoA:ACP transacylase (MAT), ketoreductase (KR) domain, and thioester reductase (TE) domains (PubMed:28381497).
The presence and positions in swnK of the 2 reductase domains, ketoeductase and thioester reductase, suggests that the intermediate released from this enzyme has a hydroxyl group (PubMed:28381497).
The presence and positions in swnK of the 2 reductase domains, ketoeductase and thioester reductase, suggests that the intermediate released from this enzyme has a hydroxyl group (PubMed:28381497).
Sequence similarities
In the N-terminal section; belongs to the NRP synthetase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length2,567
- Mass (Da)276,565
- Last updated2010-05-18 v1
- ChecksumD84E988BF522634C
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 2092-2165 | Polar residues | ||||
Sequence: STFSPKAKGVSRSNGTPKTNTTNGTSTNGTSTNGTSTNGTSTNGTHGTNGTPGSNGVSHTNGISKSNAEAKSNG |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
ABSU01000010 EMBL· GenBank· DDBJ | EFE33484.1 EMBL· GenBank· DDBJ | Genomic DNA |