D4AU31 · SWNK_ARTBC

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).

Catalytic activity

Pathway

Mycotoxin biosynthesis.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site793For beta-ketoacyl synthase activity
Active site928For beta-ketoacyl synthase activity
Active site968For beta-ketoacyl synthase activity

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentplasma membrane
Molecular Functionfatty acid synthase activity
Molecular Functionligase activity
Molecular Functionmethyltransferase activity
Molecular Functionoxidoreductase activity
Molecular Functionphosphopantetheine binding
Biological Processfatty acid biosynthetic process
Biological Processmethylation
Biological Processsecondary metabolite biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    PKS-NRPS hybrid synthetase swnK
  • EC number
  • Alternative names
    • Swainsonine biosynthesis gene cluster protein K

Gene names

    • Name
      swnK
    • ORF names
      ARB_07844

Organism names

Accessions

  • Primary accession
    D4AU31

Proteomes

Subcellular Location

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00004411781-2567PKS-NRPS hybrid synthetase swnK
Modified residue564O-(pantetheine 4'-phosphoryl)serine
Modified residue2044O-(pantetheine 4'-phosphoryl)serine

Keywords

Interaction

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, domain, compositional bias.

TypeIDPosition(s)Description
Region39-428Adenylation (A) domain
Domain529-604Carrier 1
Domain624-1047Ketosynthase family 3 (KS3)
Region1157-1478Malonyl-CoA:ACP transacylase (MAT) domain
Region1730-1908Ketoreductase (KR) domain
Domain2009-2084Carrier 2
Compositional bias2092-2165Polar residues
Region2092-2176Disordered
Region2213-2519Thioester reductase (TE) domain

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).

Sequence similarities

In the N-terminal section; belongs to the NRP synthetase family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    2,567
  • Mass (Da)
    276,565
  • Last updated
    2010-05-18 v1
  • Checksum
    D84E988BF522634C
MLNHERTSSLSDQDYQSLVYDFNAAEDVSLLGGRLDQLFEKIVDTFPKNTALIHRDTEITFSELNESANILARSLIKRGLKHGDLVGLAVSRSIDLIVVVLAVLKLGAAYVPIDPLFPAERINQMVSDAGPKLILLSGSPSKGLASWKDICISVDEARDSSIVDTTNLEADIQPHDLSYVIYTSGSTGKPKGVEISHGAAANFLSSLRKYEPGCNEHDILLAITTISFDMSALELLLPLVSGTTMVIADTTAVKNPRELLELMRRHHVTILQATPATWTMLLESGWKGDPRLSKIICGGEPLTRQLADRLLAAADSVWNVYGPSETTYGSVGRVGEGDIVVGKPVVNGRIYVLDDNLSPAPVGCEGEIYIGGGSVSNGYRNNAELTRARFLANPFHGGLFFRTGDLGRFLAPGKLQVVGRIDGVVKIRGHRIDVGDIEAVLLDHASVSAAVVISHDDRLVAYCVLDGALSSDVSLDTILRPWVAERLPAYMLPAFFVQMDALPLSPNEKVNRKALPNPLEAIQSQASKQPTSELEQQLLAIWADILGHDRFGIEDNFFNLGGDSVRIIRMQTILERLLHRPIPTPKLFEHYTIKALAAYLTGIGMESTSNQELNTANDRFIGSHEDIAIVSMACRLPGGVTTPEEFWQLLQNGGDTIIDVPKDRWDAAKLYNSNPDIEGTSYCARGGFLDSVYSYDASFFGISPREAQAMDPAQNLMLELGWESFERAGYTKERLRGSATGVFIGVSNNGTTNSTPPDLKGYSITGSASAAMSGRLSYTLGLEGPSLVVDTACSSSLVATHLACNALRQGECNMALVGGVSLLLTPGIHVEFSKLRGLSADGRCRAFSQDTDGTGFSEGATSIVLKRLSDARRDGDTIHAVLRGTAVMHGGYSAGLTVPNSPGQVKLIRSALAQGAMKPCDIDYIEAHGTATKLGDPIEATALAEVFGNGRASSDPLRLGSAKSNVGHTQAAAGLVGLLKVVLSMRYNIIPKTLHVNEPTRSVDWKGANMELVLAPQPWPPRDHRLRRAGISAFGIGGTNAHIVVEEPPKLLARKNGCTLPTLVPSAIPFLLSGGSESALKAQAEKLRLHIESGIGKDDRLIDIAFSLATTRTHLQRRQVVVSRDKAQMLDALASVSSSSDKLFNVNEVGKPKIGMLFTGQGSQRLGMGKELYSVYPVFQTSIDNIAALFTQLDIPLLNVMWAEPESTHASLLNRTDYTQAALFALEVSLWNLWQSWGVQPDFLLGHSVGEIAAAHVSGILNLSDACRLVAMRGSLMQSLPSQGKMASVEASSIEVEEVVNELSKREEVEIAGYNTPSQTVISGNSEAVEAVTAHIARMGRKTKLLDTSHAFHSAHMNGMMDAFRAVTQDLQFETAKIPIISSMTGSLAAAGEPQCAEYWVQQARRAVRFSDAFQELIKQGANVFLEIGPSSTLCGLGAACVSDISQMSKALWLPSLKPRADEVSVVQNSAHELHMRHVPINWAEYFKPFDCERVSLPTYAFQRVSYQPTTKASWLNGLTQRNDSRTVVSGVENKMFEINWRQLSVDETLPRGIWGLFNLSNATTWVIAAHQALESSGVQLVQIAKLQDAMQLDGVLVFWDSDADVVQKAHAFSTAALAHLQEASNIGFAAPIVWVTRRAVGAGVGDQPVGLGAGPLWGLMRTTRSEHPELHLRLVDVDDETSLAALGTALAADSQTEISIRKGQLLVPHLERTNLASAPAGKPLLRTDGAVLVTGGLGDLGKRVSHRLVSCHGVRDLVLLSRTGKVSARADAFIVELSKLGANVTIVRCDVSELDSLKLVMQKFTADRPLRGVIHAAGVVDSGVLSSLTPEKCATTFAPKVDGLWNLHQLTKDMDLDIFMMFSSISGIMGLPGLGNYAAANSFIDTLSYLRRSQGLPATSVAYGVWGGDGMATTLVSTTRNHLSQLGLGYLEPEDGLKLFEQGVQCGKPLTIAAVLDLERLKSYYGEQGGIPPLLRSILGEQNDKLAVNTDMSLRDLLSNAAPAQHGRIVLHIVRKAIGKALGYAQMDEIDPSQPLKELGIDSLTAILVRNHLATLTGMTLPPNVALLRPNLKSLSEFILSLLQDSTDIGSTFSPKAKGVSRSNGTPKTNTTNGTSTNGTSTNGTSTNGTSTNGTHGTNGTPGSNGVSHTNGISKSNAEAKSNGGMKANGSAPKSVPHVDMAAIKRGVLDRSFQFENITKYPLSCLNTPKAVFVTGPTGFVGAFMVHELLKRGIAVYCLIRSSNLDQAQERMTQTLREYGLWKPEYASLIHSIIGDLSQPLLGLHEDMFDELADVVDAIIHSGALVDWMRPLEDYIGPNILGTHEILRLASHGRGKAVHFVSTISTLPIHLGYGLTELDGEYGYGTSKYLAERMIVAARFRGAVASSYRLPFVAASGTNGRFRLDRGDFLNNLVMGSLDLGAFPSLNTTLSSVLPVDYLCSTIAMIMTEDQGRIGEDYDFVNPRAPTFDTFFGIMGAASGNLEVLPFSQWHRRALEYAALNPKSPLARITTVLDGYTDETAGDLLKGSPVGKHVFGLDVYPAPLVGEDYIHKYLDSINSTRQNGGL

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias2092-2165Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
ABSU01000010
EMBL· GenBank· DDBJ
EFE33484.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

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