FUMOC_CORFA
ID FUMOC_CORFA Reviewed; 394 AA.
AC A0A0E3U2K2; A0A162MAW5;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 24-JUN-2015, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Trans-enoyl reductase fumoC {ECO:0000303|PubMed:25857260};
DE EC=1.-.-.- {ECO:0000305|PubMed:25857260};
DE AltName: Full=Fumosorinone biosynthesis cluster protein C {ECO:0000303|PubMed:25857260};
GN ORFNames=ISF_08691;
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: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of fumosorinone, a 2-pyridone alkaloid that acts as an
CC inhibitor of protein tyrosine phosphatase 1B which is implicated asa
CC negative regulator of insulin receptor signaling and a potential drug
CC target for the treatment of type II diabetes and other associated
CC metabolic syndromes (PubMed:25857260). The polyketide-amino acid
CC 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 -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25857260}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=OAA53530.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; KP737857; AKC54419.1; -; Genomic_DNA.
DR EMBL; AZHB01000034; OAA53530.1; ALT_INIT; Genomic_DNA.
DR RefSeq; XP_018700481.1; XM_018852294.1.
DR AlphaFoldDB; A0A0E3U2K2; -.
DR SMR; A0A0E3U2K2; -.
DR EnsemblFungi; OAA53530; OAA53530; ISF_08691.
DR GeneID; 30024983; -.
DR OrthoDB; 727365at2759; -.
DR Proteomes; UP000076744; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..394
FT /note="Trans-enoyl reductase fumoC"
FT /id="PRO_0000451335"
FT BINDING 62..65
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 152..159
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 224..227
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 242
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 289..290
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 309..313
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 378..379
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 394 AA; 41729 MW; BC7DA85C1AA86DBA CRC64;
MRMPTNLQHP NMTAIASLPR SQNALKIVSP NTFHVDANAP LPTLVDHDSV LIRVVCVAIN
PVDGKSADLS ATAGATSGTD FAGIVVALPP DTNSEPDDDA LKIGDRVMGF VFGNNPQGRD
NGAFAEYVTV PRRLLWRLPA HMSLETAASL PASLASVGMA MHYLQIPLSS LQSAISKSIA
SSSAAAAADD EGPFVLVYGG GTSTGCMAIQ ILRLAGFVPV TCCSSSSAAR ALSLGAAATF
DYASATCGRD VREHTHDSLA LAIDCISDSA SMSICYEAIG GGGGRYVALD PFPVRGCVRR
SVVPDWICTL TQFGRPVAWA PPYNIDERPG DRRFAEEWYR LAQRMLDAHV IRAPTLETRT
GGLASVPEGI SEVRMGEVKR KKLVYNIVEQ KAAA
