SWNR_METRA
ID SWNR_METRA Reviewed; 305 AA.
AC E9F8M2;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Oxidoreductase swnR {ECO:0000303|PubMed:28381497};
DE EC=1.5.3.7 {ECO:0000305|PubMed:32786262};
DE AltName: Full=Swainsonine biosynthesis gene cluster protein R {ECO:0000303|PubMed:28381497};
GN Name=swnR {ECO:0000303|PubMed:28381497}; ORFNames=MAA_08621;
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 -!- CATALYTIC ACTIVITY:
CC Reaction=L-pipecolate + O2 = H(+) + H2O2 + L-1-piperideine-6-
CC carboxylate; Xref=Rhea:RHEA:11992, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:58769,
CC ChEBI:CHEBI:61185; EC=1.5.3.7;
CC Evidence={ECO:0000305|PubMed:32786262};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11994;
CC Evidence={ECO:0000305|PubMed:32786262};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:32786262}.
CC -!- DISRUPTION PHENOTYPE: Does not affect the production of swainsonine.
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; EFY95968.1; -; Genomic_DNA.
DR RefSeq; XP_007824810.1; XM_007826619.1.
DR AlphaFoldDB; E9F8M2; -.
DR SMR; E9F8M2; -.
DR EnsemblFungi; EFY95968; EFY95968; MAA_08621.
DR GeneID; 19262907; -.
DR KEGG; maj:MAA_08621; -.
DR HOGENOM; CLU_044876_5_0_1; -.
DR Proteomes; UP000002498; Unassembled WGS sequence.
DR GO; GO:0050031; F:L-pipecolate oxidase activity; IEA:UniProtKB-EC.
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..305
FT /note="Oxidoreductase swnR"
FT /id="PRO_0000441186"
SQ SEQUENCE 305 AA; 34289 MW; A84A44DB48957D35 CRC64;
MRVAIAGYGD LTRYICEEFV KAGHVLVILT RSYKPQLESQ GVAQAITDYS PSSLRAPLAD
CEVLISTISD ISSAYTNVHR NLILACQESP RCKRFIPAEF VADIEAYPDE PGFYYAPHEP
IREMLRGQTD LEWTLVCIGW LSDYFVPSKN RHIKDIGEFH PMNWAGNKIV IPGTGNEPVD
FTWARDVVRG LASLIEAPRG SWEPYTFMSG ERSCWNDATR LAVQKYRPGI PIQHVSLHSV
AGMIKTAKDE NTEVLADYYL LSISQACAIP TDKVEAHREK YFSGVTFRSL RDGLCQVDEH
PDSIL
