SWNH2_METRA
ID SWNH2_METRA Reviewed; 331 AA.
AC E9F8M4;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Dioxygenase swnH2 {ECO:0000303|PubMed:28381497};
DE EC=1.14.11.- {ECO:0000305|PubMed:28381497};
DE AltName: Full=Swainsonine biosynthesis gene cluster protein H2 {ECO:0000303|PubMed:28381497};
GN Name=swnH2 {ECO:0000303|PubMed:28381497}; ORFNames=MAA_08623;
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: Dioxygenase; 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 -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q4WAW9};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:32786262}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q4WAW9}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of swainsonine as well
CC as of the 1,2-dihydroxyindolizine epimers intermediates.
CC {ECO:0000269|PubMed:32786262}.
CC -!- SIMILARITY: Belongs to the PhyH family. {ECO:0000305}.
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DR EMBL; ADNJ02000001; EFY95970.1; -; Genomic_DNA.
DR RefSeq; XP_007824812.1; XM_007826621.1.
DR AlphaFoldDB; E9F8M4; -.
DR SMR; E9F8M4; -.
DR EnsemblFungi; EFY95970; EFY95970; MAA_08623.
DR GeneID; 19262909; -.
DR KEGG; maj:MAA_08623; -.
DR HOGENOM; CLU_047725_0_0_1; -.
DR Proteomes; UP000002498; Unassembled WGS sequence.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 3: Inferred from homology;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT CHAIN 1..331
FT /note="Dioxygenase swnH2"
FT /id="PRO_0000441184"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 173
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 175
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 250
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
SQ SEQUENCE 331 AA; 37049 MW; 2E78351D29AC0A88 CRC64;
MINSDAQSAQ KQVEVEKPDE KYSAPRLLPP IPDSYQPAKA ITKIPATSSL EDILAILERD
GGVILTDFVS LQELDKIDEE LEPYTKSSIA DDDSYNNFIG KKTLVIPGLV GKSDTIANIL
DTNETIDKLL KVILEERYPA VFEQHTEELV VDPLLSICMG FHVGHGSPRQ ALHRDDMIFS
SKHRPDMKIN EVDGFSCFLA GTRITRENGG TMVILGSHKW EHDRRGRPDE VSFLEMERGS
AFIFLSTLAH GAGYNTIPGE VRKITNLVFC RGTLRTEENQ FLCVPRSKVL KMSPKMQTLL
GFKKPAGSWL GMVENEDPAK DLEAIYEKML K
