SUBE_METRA
ID SUBE_METRA Reviewed; 322 AA.
AC E9F5F0;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 04-MAR-2015, sequence version 2.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=FAD-dependent monooxygenase subE {ECO:0000303|PubMed:27189118};
DE EC=1.-.-.- {ECO:0000305|PubMed:27189118};
DE AltName: Full=Subglutinol biosynthesis cluster protein E {ECO:0000303|PubMed:27189118};
GN Name=subE {ECO:0000303|PubMed:27189118}; ORFNames=MAA_07499;
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=27189118; DOI=10.1038/ja.2016.54;
RA Kato H., Tsunematsu Y., Yamamoto T., Namiki T., Kishimoto S., Noguchi H.,
RA Watanabe K.;
RT "New natural products isolated from Metarhizium robertsii ARSEF 23 by
RT chemical screening and identification of the gene cluster through
RT engineered biosynthesis in Aspergillus nidulans A1145.";
RL J. Antibiot. 69:561-566(2016).
CC -!- FUNCTION: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the immunosuppressants subglutinols,
CC meroterpenoids consisting of an alpha-pyrone (4-hydroxy-5,6-dimethyl-2-
CC pyrone) moiety attached to a decalin core fused to a five-membered
CC cyclic ether carrying a prenylside chain (PubMed:27189118). The first
CC step of the pathway is the synthesis of the alpha-pyrone moiety by the
CC polyketide synthase subA via condensation of one acetyl-CoA starter
CC unit with 3 malonyl-CoA units and 2 methylations (PubMed:27189118). The
CC alpha-pyrone is then combined with geranylgeranyl pyrophosphate (GGPP)
CC formed by the GGPP synthase subD through the action of the
CC prenyltransferase subC to yield a linear alpha-pyrone diterpenoid
CC (PubMed:27189118). Subsequent steps in the subglutinol biosynthetic
CC pathway involve the decalin core formation, which is thought to be
CC initiated by the epoxidation of the C10-C11 olefin by the FAD-dependent
CC oxidoreductase subE (Probable). The following cyclization cascade would
CC be catalyzed by the terpene cyclase subB (Probable). Lastly, the FAD-
CC dependent dehydrogenase subF probably catalyzes the five-membered
CC cyclic ether formation to complete the formation of subglutinol A
CC (Probable). Subsequent redox reactions appear to give rise to
CC subglutinol C and D, however, it remains unclear which enzymes are
CC responsible for these transformations (Probable).
CC {ECO:0000269|PubMed:27189118, ECO:0000305|PubMed:27189118}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000305};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:27189118}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; ADNJ02000014; EFY96953.2; -; Genomic_DNA.
DR RefSeq; XP_007823688.2; XM_007825497.2.
DR AlphaFoldDB; E9F5F0; -.
DR SMR; E9F5F0; -.
DR EnsemblFungi; EFY96953; EFY96953; MAA_07499.
DR GeneID; 19261785; -.
DR KEGG; maj:MAA_07499; -.
DR HOGENOM; CLU_009665_12_1_1; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000002498; Unassembled WGS sequence.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT CHAIN 1..322
FT /note="FAD-dependent monooxygenase subE"
FT /id="PRO_0000451341"
FT BINDING 36..37
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 313
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 322 AA; 36046 MW; AA17C6F5D2B2713D CRC64;
MSQRQFKVII IGGSVTGLTL AHSLHKIGID YVVLEKRDTV TPQEGASIGI LPNGARILDQ
LGLYEAIEDE APPLGATRIH FPDGFAFTSL YPKKILENFG YPIAFLERRQ LLRILYDALP
DKTRIHVNKT MSTIEHFTKD EITGARVLTK EGDVYEGDLI VGADGIHSQT RGEIWRRINS
SKSEFEPAEC IDKCILIEYS CCFGISKCVT GLIAGEQVMH MRNGRTLVVI PSKDEVVFWF
LVEKLDRKYT YSEAPRFTID DATALCSQVF TLPIGNGIKF EDVWNKREVV NMLSLEESCL
STWSTGRLVC IGDSIHKVSI PS
