ID   SUBF_METRA              Reviewed;         509 AA.
AC   E9F5F1;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   05-APR-2011, sequence version 1.
DT   25-MAY-2022, entry version 42.
DE   RecName: Full=FAD-linked oxidoreductase subF {ECO:0000303|PubMed:27189118};
DE            EC=1.1.1.- {ECO:0000305|PubMed:27189118};
DE   AltName: Full=Subglutinol biosynthesis cluster protein E {ECO:0000303|PubMed:27189118};
DE   Flags: Precursor;
GN   Name=subF {ECO:0000303|PubMed:27189118}; ORFNames=MAA_07500;
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-linked oxidoreductase; 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 oxygen-dependent FAD-linked oxidoreductase
CC       family. {ECO:0000305}.
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DR   EMBL; ADNJ02000014; EFY96954.1; -; Genomic_DNA.
DR   RefSeq; XP_007823689.1; XM_007825498.1.
DR   AlphaFoldDB; E9F5F1; -.
DR   SMR; E9F5F1; -.
DR   EnsemblFungi; EFY96954; EFY96954; MAA_07500.
DR   GeneID; 19261786; -.
DR   KEGG; maj:MAA_07500; -.
DR   HOGENOM; CLU_018354_10_1_1; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000002498; Unassembled WGS sequence.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 3.30.465.10; -; 1.
DR   InterPro; IPR012951; BBE.
DR   InterPro; IPR016166; FAD-bd_PCMH.
DR   InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR   InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR   InterPro; IPR006094; Oxid_FAD_bind_N.
DR   Pfam; PF08031; BBE; 1.
DR   Pfam; PF01565; FAD_binding_4; 1.
DR   SUPFAM; SSF56176; SSF56176; 1.
DR   PROSITE; PS51387; FAD_PCMH; 1.
PE   3: Inferred from homology;
KW   FAD; Flavoprotein; Glycoprotein; Oxidoreductase; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..509
FT                   /note="FAD-linked oxidoreductase subF"
FT                   /id="PRO_5003239953"
FT   DOMAIN          59..231
FT                   /note="FAD-binding PCMH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT   CARBOHYD        125
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        281
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   509 AA;  55264 MW;  59236F4CAB6989E5 CRC64;
     MTRLSLQIIA GLAGQAWLVN SDTPSHDAFA SCLSDASVPI ATKGTPEWTQ HTTPFNTRLQ
     YEPIAVAVPT EISQIAAAVT CAKTNGIPVT AKSGGHSFTS LGLGGEDGHL VIQLDRMYNV
     ELAQNGTAMI QAGARLGHVA VELYNQGKRA LSHGYCPAVG VGGHAAHGGY GMVSRKYGLT
     LDWMKDATVV LHNGTIVYCS ESEHSDLFWA IRGAGSSFGI VAEYGFETFP APEKVTNFGI
     VLDWNPETAP AGLLAFQDFA QTMPSELSCQ IDVRSTGYTL NGSYVGNEAS LREALVPLLG
     KIGGHLEVHE GNWLEYVKFW ALGQPNIDIT PPADNVHLSL YTTGALTPSL SANQFRSFAD
     YIATDAIKRG NSWSIQMFIH GGQYSAISGP KITDTAYAHR DKFLIFQFTD FVWPSQEYPE
     DGLALGREFR DIITNSFTNG QWGMYANVPD SQLSSGEAQK LYWGKNLERL ETIKAKYDPN
     NLFRNPQSVK AAARCATRPL PLQGQSLLF