FUMOA_CORFA
ID FUMOA_CORFA Reviewed; 509 AA.
AC A0A167LUS5; A0A0E3U216;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 06-JUL-2016, sequence version 1.
DT 03-AUG-2022, entry version 21.
DE RecName: Full=Cytochrome P450 monooxygenase fumoA {ECO:0000303|PubMed:25857260};
DE EC=1.-.-.- {ECO:0000305|PubMed:25857260};
DE AltName: Full=Fumosorinone biosynthesis cluster protein A {ECO:0000303|PubMed:25857260};
GN Name=fumoA {ECO:0000303|PubMed:25857260}; ORFNames=ISF_08693;
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; AKC54420.1; -; Genomic_DNA.
DR EMBL; AZHB01000034; OAA53532.1; -; Genomic_DNA.
DR RefSeq; XP_018700483.1; XM_018852296.1.
DR AlphaFoldDB; A0A167LUS5; -.
DR SMR; A0A167LUS5; -.
DR STRING; 1081104.A0A167LUS5; -.
DR EnsemblFungi; OAA53532; OAA53532; ISF_08693.
DR GeneID; 30024985; -.
DR OrthoDB; 1247045at2759; -.
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:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002974; Cyt_P450_E_CYP52.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR01239; EP450IICYP52.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 3: Inferred from homology;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..509
FT /note="Cytochrome P450 monooxygenase fumoA"
FT /id="PRO_0000451333"
FT TRANSMEM 5..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 456
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 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 509 AA; 58931 MW; 95264BCC5C08DD3E CRC64;
MVATLANLNF PYLILSACLS AILLSRFLPF TRRDRRPTAK GCLPEPRVFQ WDVFFGLDIP
ISQGRALQQN RYLEWLRDLH ASMPRTKTFS VNFGGYRWIY SIEPEILKAV YATNFQDFGV
EPIRQHPPGF KPFAEKGVST SDGEDWAFSR SLIKPFFERS VYVSTDRVKP FADKFLTFIP
EDGETFDIQP LLQRWFLDMT SEFIFGKSQD SMTHPERAEV IWAMADVLRG TRLRAQTYKI
LWAFNWDWWF KAIEKVHGFL NPYIRSTLAE LAERQQRVKE GLPVGEERTD LLWSMATMLP
EEEALRSQVC IIFVPNNDTT SIFIAHCLYF LARHPDAWRK LREEVTAVGD APITFELLRN
MKYLNGIMNE THRLIPNNVT QIRSALSDVV LPLGGGPDGK APLDVRKGDI VSVTKTVMYR
DPDRWGADAD EYRPERWDGM RGGWHFLPYG GGPRRCPAQM MVQNESGYML CRLARRYARI
EARDKEPYRA RMRIGPSSLH GVKIAFYKE
