FUMOB_CORFA
ID FUMOB_CORFA Reviewed; 546 AA.
AC A0A167LUR6; A0A0E3Y591;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 06-JUL-2016, sequence version 1.
DT 03-AUG-2022, entry version 26.
DE RecName: Full=Cytochrome P450 monooxygenase fumoB {ECO:0000303|PubMed:25857260};
DE EC=1.-.-.- {ECO:0000305|PubMed:25857260};
DE AltName: Full=Fumosorinone biosynthesis cluster protein B {ECO:0000303|PubMed:25857260};
GN Name=fumoB {ECO:0000303|PubMed:25857260}; ORFNames=ISF_08692;
OS Cordyceps fumosorosea (strain ARSEF 2679) (Isaria fumosorosea).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Cordycipitaceae; Cordyceps.
OX NCBI_TaxID=1081104;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=ARSEF 2679;
RX PubMed=25857260; DOI=10.1016/j.fgb.2015.03.009;
RA Liu L., Zhang J., Chen C., Teng J., Wang C., Luo D.;
RT "Structure and biosynthesis of fumosorinone, a new protein tyrosine
RT phosphatase 1B inhibitor firstly isolated from the entomogenous fungus
RT Isaria fumosorosea.";
RL Fungal Genet. Biol. 81:191-200(2015).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ARSEF 2679;
RX PubMed=27071652; DOI=10.1093/gbe/evw082;
RA Shang Y., Xiao G., Zheng P., Cen K., Zhan S., Wang C.;
RT "Divergent and convergent evolution of fungal pathogenicity.";
RL Genome Biol. Evol. 8:1374-1387(2016).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of fumosorinone, a 2-pyridone alkaloid that
CC acts as an inhibitor of protein tyrosine phosphatase 1B which is
CC implicated asa negative regulator of insulin receptor signaling and a
CC potential drug target for the treatment of type II diabetes and other
CC associated metabolic syndromes (PubMed:25857260). The polyketide-amino
CC acid backbone of fumosorinone is first assembled by the PKS-NRPS hybrid
CC fumoS (PubMed:25857260). The PKS modules condense one acetyl-CoA
CC starter unit with 7 malonyl-CoA units, programmed C-methylations
CC occurring after the first 3 and the sixth extensions, and cycles of
CC full reduction occurring after the first 2 extensions (Probable).
CC Because fumoS lacks a designated enoyl reductase (ER) domain, the
CC required activity is provided the enoyl reductase fumoC (Probable).
CC Upon formation of the polyketide backbone on the thiotemplate, the
CC polyketide is transferred to the NRPS module and linked to tyrosine to
CC produce the acyltetramic acid intermediate called prefumosorinone A
CC (Probable). The cytochrome P450 monooxygenase fumoA then probably
CC catalyzes an unprecedented oxidative ring expansion of prefumosorinone
CC A to form prefumosorinone B which contains the 2-pyridone core of
CC fumosorinone (Probable). The cytochrome P450 monooxygenase fumoB might
CC hydroxylate the nitrogen of prefumosorinone B, but not the acyltetramic
CC acid prefumosorinone A, to form fumosorinone (Probable).
CC {ECO:0000269|PubMed:25857260, ECO:0000305,
CC ECO:0000305|PubMed:25857260}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25857260}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KP737857; AKC54421.1; -; Genomic_DNA.
DR EMBL; AZHB01000034; OAA53531.1; -; Genomic_DNA.
DR RefSeq; XP_018700482.1; XM_018852295.1.
DR AlphaFoldDB; A0A167LUR6; -.
DR SMR; A0A167LUR6; -.
DR EnsemblFungi; OAA53531; OAA53531; ISF_08692.
DR GeneID; 30024984; -.
DR OrthoDB; 595327at2759; -.
DR Proteomes; UP000076744; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..546
FT /note="Cytochrome P450 monooxygenase fumoB"
FT /id="PRO_0000451334"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 488
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 546 AA; 61141 MW; 97A39E22F26CFEC1 CRC64;
MALSAAASTL ARLGYYEKLA GILGIIGLVL LFWQRTRQPF YPDLPLAGET PHRRWFSLRT
RFRYYTDCAS LFNEAYHTVR FHASTSSSST LSRLNAHASQ YTKHGKGVLL PSVGVHTAVV
MPESALDWAM SQPDSALSIT HAFADLNQTR YSLGDARYWR DPWQLTLVKA HLAAVTPALV
PQLNDELADA LAKRLGTDTD SWREMELETT LRRVVAQTLS RLIVGPELCR DEGYLDLAYK
VVLGVMTTIF ATLPYPDLVR AVTGPLASWH TQRRISRIQR HLEPLYRERL AILRSAKEDQ
PPDLLMAMMR FAQKKRPEEL ADPAIIARRV CAANFVAMHQ TTIVLTNIIL HVLGSDAEFS
TIAALRSEAA AHLLSSERIT KDAFAQMKVA DSVAREATRL NFPLGGRASP RTVMRDGLVS
PEGIRLQRGT TVSWLAGCAQ LDPEAFPEPR RFDPFRFSRG DGDGEGERDT FVKTSARYLP
WGHGKHACPG RFVVDYVVKM ALAQLVTKYD LAWPEDYGGK QPPSVWLAEL SVPPPRARIM
VRRRKV
