SWNK_ARTBC
ID SWNK_ARTBC Reviewed; 2567 AA.
AC D4AU31;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=PKS-NRPS hybrid synthetase swnK {ECO:0000303|PubMed:28381497};
DE EC=2.3.1.- {ECO:0000305|PubMed:28381497};
DE AltName: Full=Swainsonine biosynthesis gene cluster protein K {ECO:0000303|PubMed:28381497};
GN Name=swnK {ECO:0000303|PubMed:28381497}; ORFNames=ARB_07844;
OS Arthroderma benhamiae (strain ATCC MYA-4681 / CBS 112371) (Trichophyton
OS mentagrophytes).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Onygenales; Arthrodermataceae; Trichophyton.
OX NCBI_TaxID=663331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4681 / CBS 112371;
RX PubMed=21247460; DOI=10.1186/gb-2011-12-1-r7;
RA Burmester A., Shelest E., Gloeckner G., Heddergott C., Schindler S.,
RA Staib P., Heidel A., Felder M., Petzold A., Szafranski K., Feuermann M.,
RA Pedruzzi I., Priebe S., Groth M., Winkler R., Li W., Kniemeyer O.,
RA Schroeckh V., Hertweck C., Hube B., White T.C., Platzer M., Guthke R.,
RA Heitman J., Woestemeyer J., Zipfel P.F., Monod M., Brakhage A.A.;
RT "Comparative and functional genomics provide insights into the
RT pathogenicity of dermatophytic fungi.";
RL Genome Biol. 12:R7.1-R7.16(2011).
RN [2]
RP IDENTIFICATION, DOMAIN, AND PATHWAY.
RX PubMed=28381497; DOI=10.1534/g3.117.041384;
RA Cook D., Donzelli B.G., Creamer R., Baucom D.L., Gardner D.R., Pan J.,
RA Moore N., Jaromczyk J.W., Schardl C.L.;
RT "Swainsonine biosynthesis genes in diverse symbiotic and pathogenic
RT fungi.";
RL G3 (Bethesda) 7:1791-1797(2017).
CC -!- FUNCTION: PKS-NRPS hybrid synthetase; part of the gene cluster that
CC mediates the biosynthesis of swainsonine (SW), a cytotoxic fungal
CC alkaloid and a potential cancer therapy drug (PubMed:28381497).
CC Swainsonine production occurs via a multibranched pathway and is
CC dispensable for fungal colonization of plants and infection of insect
CC hosts (By similarity). The first step of swainsonine biosynthesis is
CC the production of the precursor pipecolic acid (PA) via conversion of
CC L-lysine (Lys) to 1-piperideine-6-carboxylate (P6C) by the
CC aminotransferase swnA, the latter being further reduced to PA by the
CC reductase swnR (By similarity). The PKS-NRPS hybrid synthetase swnK
CC uptakes and condensates PA and malonyl-CoA with and without skipping of
CC the ketoreductase (KR) domain in order to produce 3 intermediates, 1-
CC oxoindolizidine, (1S)-1-hydroxyindolizin, and (1R)-1-hydroxyindolizine;
CC with the transisomer (1S)-1-hydroxyindolizin being predominant (By
CC similarity). The terminal thioester reductase (TE) domain of swnK is
CC involved in reduction of the thioester bond to release the intermediate
CC aldehydes (By similarity). The oxidoreductase swnN could contribute to
CC the reduction of 1-oxoindolizidine to (1S)-1-hydroxyindolizin and (1R)-
CC 1-hydroxyindolizine, contributing to the major route of SW production
CC (By similarity). The dioxygenase swnH2 would be responsible for the
CC oxidization of (1R)-1-hydroxyindolizine into (1R,2S)-1,2-
CC dihydroxyindolizine and of (1S)-1-hydroxyindolizin to yield both
CC (1R,2S)-1,2-dihydroxyindolizine and (1S,2S)-1,2-dihydroxyindolizine (By
CC similarity). The dioxygenase swnH1 then performs the conversion of the
CC 1,2-dihydroxyindolizine epimers to SW (By similarity).
CC {ECO:0000250|UniProtKB:E9F8L8, ECO:0000250|UniProtKB:E9F8L9,
CC ECO:0000250|UniProtKB:E9F8M1, ECO:0000250|UniProtKB:E9F8M3,
CC ECO:0000250|UniProtKB:E9F8M4, ECO:0000269|PubMed:28381497}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 H(+) + L-pipecolate + malonyl-CoA + 2 NADPH = (8aS)-
CC octahydroindolizin-1-one + CO2 + CoA + 2 H2O + 2 NADP(+);
CC Xref=Rhea:RHEA:65392, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:61185,
CC ChEBI:CHEBI:167645; Evidence={ECO:0000250|UniProtKB:E9F8M3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65393;
CC Evidence={ECO:0000250|UniProtKB:E9F8M3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5 H(+) + L-pipecolate + malonyl-CoA + 3 NADPH = (1R,8aS)-
CC octahydroindolizin-1-ol + CO2 + CoA + 2 H2O + 3 NADP(+);
CC Xref=Rhea:RHEA:67128, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:61185,
CC ChEBI:CHEBI:167675; Evidence={ECO:0000250|UniProtKB:E9F8M3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67129;
CC Evidence={ECO:0000250|UniProtKB:E9F8M3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5 H(+) + L-pipecolate + malonyl-CoA + 3 NADPH = (1S,8aS)-
CC octahydroindolizin-1-ol + CO2 + CoA + 2 H2O + 3 NADP(+);
CC Xref=Rhea:RHEA:67132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:61185,
CC ChEBI:CHEBI:167676; Evidence={ECO:0000250|UniProtKB:E9F8M3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67133;
CC Evidence={ECO:0000250|UniProtKB:E9F8M3};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:28381497}.
CC -!- DOMAIN: The architecture of swnK is the following one: adenylation (A),
CC phosphopantetheine-binding/thiolation (T), beta-ketoacyl synthase (KS),
CC malonyl-CoA:ACP transacylase (MAT), ketoreductase (KR) domain, and
CC thioester reductase (TE) domains (PubMed:28381497). The presence and
CC positions in swnK of the 2 reductase domains, ketoeductase and
CC thioester reductase, suggests that the intermediate released from this
CC enzyme has a hydroxyl group (PubMed:28381497).
CC {ECO:0000305|PubMed:28381497}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; ABSU01000010; EFE33484.1; -; Genomic_DNA.
DR RefSeq; XP_003014124.1; XM_003014078.1.
DR AlphaFoldDB; D4AU31; -.
DR SMR; D4AU31; -.
DR STRING; 663331.D4AU31; -.
DR EnsemblFungi; EFE33484; EFE33484; ARB_07844.
DR GeneID; 9521541; -.
DR KEGG; abe:ARB_07844; -.
DR eggNOG; KOG1178; Eukaryota.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_1_1_1; -.
DR OMA; PLWGLMR; -.
DR Proteomes; UP000008866; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0009058; P:biosynthetic process; IEA:UniProt.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR010080; Thioester_reductase-like_dom.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 2.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 3.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR TIGRFAMs; TIGR01746; Thioester-redct; 1.
DR PROSITE; PS00455; AMP_BINDING; 2.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2567
FT /note="PKS-NRPS hybrid synthetase swnK"
FT /id="PRO_0000441178"
FT DOMAIN 529..604
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 2009..2084
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 39..428
FT /note="Adenylation (A) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28381497"
FT REGION 627..1050
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28381497"
FT REGION 1157..1478
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28381497"
FT REGION 1730..1908
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28381497"
FT REGION 2092..2176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2213..2519
FT /note="Thioester reductase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28381497"
FT COMPBIAS 2092..2165
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 564
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2044
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2567 AA; 276565 MW; D84E988BF522634C CRC64;
MLNHERTSSL SDQDYQSLVY DFNAAEDVSL LGGRLDQLFE KIVDTFPKNT ALIHRDTEIT
FSELNESANI LARSLIKRGL KHGDLVGLAV SRSIDLIVVV LAVLKLGAAY VPIDPLFPAE
RINQMVSDAG PKLILLSGSP SKGLASWKDI CISVDEARDS SIVDTTNLEA DIQPHDLSYV
IYTSGSTGKP KGVEISHGAA ANFLSSLRKY EPGCNEHDIL LAITTISFDM SALELLLPLV
SGTTMVIADT TAVKNPRELL ELMRRHHVTI LQATPATWTM LLESGWKGDP RLSKIICGGE
PLTRQLADRL LAAADSVWNV YGPSETTYGS VGRVGEGDIV VGKPVVNGRI YVLDDNLSPA
PVGCEGEIYI GGGSVSNGYR NNAELTRARF LANPFHGGLF FRTGDLGRFL APGKLQVVGR
IDGVVKIRGH RIDVGDIEAV LLDHASVSAA VVISHDDRLV AYCVLDGALS SDVSLDTILR
PWVAERLPAY MLPAFFVQMD ALPLSPNEKV NRKALPNPLE AIQSQASKQP TSELEQQLLA
IWADILGHDR FGIEDNFFNL GGDSVRIIRM QTILERLLHR PIPTPKLFEH YTIKALAAYL
TGIGMESTSN QELNTANDRF IGSHEDIAIV SMACRLPGGV TTPEEFWQLL QNGGDTIIDV
PKDRWDAAKL YNSNPDIEGT SYCARGGFLD SVYSYDASFF GISPREAQAM DPAQNLMLEL
GWESFERAGY TKERLRGSAT GVFIGVSNNG TTNSTPPDLK GYSITGSASA AMSGRLSYTL
GLEGPSLVVD TACSSSLVAT HLACNALRQG ECNMALVGGV SLLLTPGIHV EFSKLRGLSA
DGRCRAFSQD TDGTGFSEGA TSIVLKRLSD ARRDGDTIHA VLRGTAVMHG GYSAGLTVPN
SPGQVKLIRS ALAQGAMKPC DIDYIEAHGT ATKLGDPIEA TALAEVFGNG RASSDPLRLG
SAKSNVGHTQ AAAGLVGLLK VVLSMRYNII PKTLHVNEPT RSVDWKGANM ELVLAPQPWP
PRDHRLRRAG ISAFGIGGTN AHIVVEEPPK LLARKNGCTL PTLVPSAIPF LLSGGSESAL
KAQAEKLRLH IESGIGKDDR LIDIAFSLAT TRTHLQRRQV VVSRDKAQML DALASVSSSS
DKLFNVNEVG KPKIGMLFTG QGSQRLGMGK ELYSVYPVFQ TSIDNIAALF TQLDIPLLNV
MWAEPESTHA SLLNRTDYTQ AALFALEVSL WNLWQSWGVQ PDFLLGHSVG EIAAAHVSGI
LNLSDACRLV AMRGSLMQSL PSQGKMASVE ASSIEVEEVV NELSKREEVE IAGYNTPSQT
VISGNSEAVE AVTAHIARMG RKTKLLDTSH AFHSAHMNGM MDAFRAVTQD LQFETAKIPI
ISSMTGSLAA AGEPQCAEYW VQQARRAVRF SDAFQELIKQ GANVFLEIGP SSTLCGLGAA
CVSDISQMSK ALWLPSLKPR ADEVSVVQNS AHELHMRHVP INWAEYFKPF DCERVSLPTY
AFQRVSYQPT TKASWLNGLT QRNDSRTVVS GVENKMFEIN WRQLSVDETL PRGIWGLFNL
SNATTWVIAA HQALESSGVQ LVQIAKLQDA MQLDGVLVFW DSDADVVQKA HAFSTAALAH
LQEASNIGFA APIVWVTRRA VGAGVGDQPV GLGAGPLWGL MRTTRSEHPE LHLRLVDVDD
ETSLAALGTA LAADSQTEIS IRKGQLLVPH LERTNLASAP AGKPLLRTDG AVLVTGGLGD
LGKRVSHRLV SCHGVRDLVL LSRTGKVSAR ADAFIVELSK LGANVTIVRC DVSELDSLKL
VMQKFTADRP LRGVIHAAGV VDSGVLSSLT PEKCATTFAP KVDGLWNLHQ LTKDMDLDIF
MMFSSISGIM GLPGLGNYAA ANSFIDTLSY LRRSQGLPAT SVAYGVWGGD GMATTLVSTT
RNHLSQLGLG YLEPEDGLKL FEQGVQCGKP LTIAAVLDLE RLKSYYGEQG GIPPLLRSIL
GEQNDKLAVN TDMSLRDLLS NAAPAQHGRI VLHIVRKAIG KALGYAQMDE IDPSQPLKEL
GIDSLTAILV RNHLATLTGM TLPPNVALLR PNLKSLSEFI LSLLQDSTDI GSTFSPKAKG
VSRSNGTPKT NTTNGTSTNG TSTNGTSTNG TSTNGTHGTN GTPGSNGVSH TNGISKSNAE
AKSNGGMKAN GSAPKSVPHV DMAAIKRGVL DRSFQFENIT KYPLSCLNTP KAVFVTGPTG
FVGAFMVHEL LKRGIAVYCL IRSSNLDQAQ ERMTQTLREY GLWKPEYASL IHSIIGDLSQ
PLLGLHEDMF DELADVVDAI IHSGALVDWM RPLEDYIGPN ILGTHEILRL ASHGRGKAVH
FVSTISTLPI HLGYGLTELD GEYGYGTSKY LAERMIVAAR FRGAVASSYR LPFVAASGTN
GRFRLDRGDF LNNLVMGSLD LGAFPSLNTT LSSVLPVDYL CSTIAMIMTE DQGRIGEDYD
FVNPRAPTFD TFFGIMGAAS GNLEVLPFSQ WHRRALEYAA LNPKSPLARI TTVLDGYTDE
TAGDLLKGSP VGKHVFGLDV YPAPLVGEDY IHKYLDSINS TRQNGGL
