SWNN_METRA
ID SWNN_METRA Reviewed; 341 AA.
AC E9F8M1;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Oxidoreductase swnN {ECO:0000303|PubMed:28381497};
DE EC=1.3.1.- {ECO:0000305|PubMed:28381497};
DE AltName: Full=Swainsonine biosynthesis gene cluster protein N {ECO:0000303|PubMed:28381497};
GN Name=swnN {ECO:0000303|PubMed:28381497}; ORFNames=MAA_08620;
OS Metarhizium robertsii (strain ARSEF 23 / ATCC MYA-3075) (Metarhizium
OS anisopliae (strain ARSEF 23)).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Metarhizium.
OX NCBI_TaxID=655844;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ARSEF 23 / ATCC MYA-3075;
RX PubMed=21253567; DOI=10.1371/journal.pgen.1001264;
RA Gao Q., Jin K., Ying S.-H., Zhang Y., Xiao G., Shang Y., Duan Z., Hu X.,
RA Xie X.-Q., Zhou G., Peng G., Luo Z., Huang W., Wang B., Fang W., Wang S.,
RA Zhong Y., Ma L.-J., St Leger R.J., Zhao G.-P., Pei Y., Feng M.-G., Xia Y.,
RA Wang C.;
RT "Genome sequencing and comparative transcriptomics of the model
RT entomopathogenic fungi Metarhizium anisopliae and M. acridum.";
RL PLoS Genet. 7:E1001264-E1001264(2011).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ARSEF 23 / ATCC MYA-3075;
RX PubMed=25368161; DOI=10.1073/pnas.1412662111;
RA Hu X., Xiao G., Zheng P., Shang Y., Su Y., Zhang X., Liu X., Zhan S.,
RA St Leger R.J., Wang C.;
RT "Trajectory and genomic determinants of fungal-pathogen speciation and host
RT adaptation.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:16796-16801(2014).
RN [3]
RP FUNCTION, 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).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=32786262; DOI=10.1021/acschembio.0c00466;
RA Luo F., Hong S., Chen B., Yin Y., Tang G., Hu F., Zhang H., Wang C.;
RT "Unveiling of Swainsonine Biosynthesis via a Multibranched Pathway in
RT Fungi.";
RL ACS Chem. Biol. 15:2476-2484(2020).
CC -!- FUNCTION: Oxidoreductase; part of the gene cluster that mediates the
CC biosynthesis of swainsonine (SW), a cytotoxic fungal alkaloid and a
CC potential cancer therapy drug (PubMed:28381497, PubMed:32786262).
CC Swainsonine production occurs via a multibranched pathway and is
CC dispensable for fungal colonization of plants and infection of insect
CC hosts (PubMed:32786262). 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 (PubMed:32786262). PA can be converted from lysine by
CC both the SW biosynthetic cluster and the unclustered genes such as
CC lysine cyclodeaminase (PubMed:32786262). The PKS-NRPS hybrid synthetase
CC swnK uptakes and condensates PA and malonyl-CoA with and without
CC skipping of the ketoreductase (KR) domain in order to produce 3
CC intermediates, 1-oxoindolizidine, (1S)-1-hydroxyindolizin, and (1R)-1-
CC hydroxyindolizine; with the transisomer (1S)-1-hydroxyindolizin being
CC predominant (PubMed:32786262). The terminal thioester reductase (TE)
CC domain of swnK is involved in reduction of the thioester bond to
CC release the intermediate aldehydes (PubMed:32786262). The
CC oxidoreductase swnN could contribute to the reduction of 1-
CC oxoindolizidine to (1S)-1-hydroxyindolizin and (1R)-1-
CC hydroxyindolizine, contributing to the major route of SW production
CC (Probable). 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
CC (PubMed:32786262). The dioxygenase swnH1 then performs the conversion
CC of the 1,2-dihydroxyindolizine epimers to SW (PubMed:32786262).
CC {ECO:0000269|PubMed:28381497, ECO:0000269|PubMed:32786262,
CC ECO:0000305|PubMed:32786262}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:32786262}.
CC -!- DISRUPTION PHENOTYPE: Leads to higher level of PA accumulation.
CC {ECO:0000269|PubMed:32786262}.
CC -!- SIMILARITY: Belongs to the NmrA-type oxidoreductase family. Isoflavone
CC reductase subfamily. {ECO:0000305}.
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DR EMBL; ADNJ02000001; EFY95967.1; -; Genomic_DNA.
DR RefSeq; XP_007824809.1; XM_007826618.1.
DR AlphaFoldDB; E9F8M1; -.
DR SMR; E9F8M1; -.
DR EnsemblFungi; EFY95967; EFY95967; MAA_08620.
DR GeneID; 19262906; -.
DR KEGG; maj:MAA_08620; -.
DR HOGENOM; CLU_044876_0_0_1; -.
DR Proteomes; UP000002498; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0044281; P:small molecule metabolic process; IEA:UniProt.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF13460; NAD_binding_10; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW NADP; Oxidoreductase.
FT CHAIN 1..341
FT /note="Oxidoreductase swnN"
FT /id="PRO_0000441188"
SQ SEQUENCE 341 AA; 37835 MW; 95191BB9B1700BEA CRC64;
MVVVAVAGGT GGVGRTVLDA IAKSGQHQAI VLSRTTSVPT AVDEPKRFAV DYNSVEQMKK
ILQENNVQVV VSALLLVDEA VAQSQINLIR AAAQSGTVTK FIPSEYYIDF HAPIPYVSLQ
SILSRQRFSL FSTSGADLFT NFQLEAEAEL SRHAQLTWTL IRVGIFLDHL TMPHNPKTTY
ITPFWVFVDI DHEQCVFPGD GSQPLVLTHS QDLAAYIERL VGLPAENWPR ESVVASNKLL
VKDLESLVNK VTGKKFKVAY DSVECIHKGR ITQLPSNTAV FQDPAKGEMF RDVEHQVMLS
MLSRAHDLPG KNLAELFPEV ETTDIEDFFR SGWTLKQSRA P
