FGOX3_PENRF
ID FGOX3_PENRF Reviewed; 369 AA.
AC W6Q9S9;
DT 20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=Chanoclavine-I aldehyde reductase fgaOx3 {ECO:0000303|PubMed:28902217};
DE EC=1.3.1.100 {ECO:0000269|PubMed:28902217};
DE AltName: Full=Isofumigaclavine biosynthesis protein fgaOx3 {ECO:0000303|PubMed:28902217};
DE AltName: Full=Old yellow enzyme homolog fgaOx3 {ECO:0000303|PubMed:28902217};
DE Short=OYE fgaOx3 {ECO:0000303|PubMed:28902217};
GN Name=fgaOx3 {ECO:0000303|PubMed:28902217}; ORFNames=PROQFM164_S03g000127;
OS Penicillium roqueforti (strain FM164).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=1365484;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FM164;
RX PubMed=24407037; DOI=10.1038/ncomms3876;
RA Cheeseman K., Ropars J., Renault P., Dupont J., Gouzy J., Branca A.,
RA Abraham A.L., Ceppi M., Conseiller E., Debuchy R., Malagnac F., Goarin A.,
RA Silar P., Lacoste S., Sallet E., Bensimon A., Giraud T., Brygoo Y.;
RT "Multiple recent horizontal transfers of a large genomic region in cheese
RT making fungi.";
RL Nat. Commun. 5:2876-2876(2014).
RN [2]
RP FUNCTION.
RX PubMed=28620689; DOI=10.1007/s00253-017-8366-6;
RA Fernandez-Bodega A., Alvarez-Alvarez R., Liras P., Martin J.F.;
RT "Silencing of a second dimethylallyltryptophan synthase of Penicillium
RT roqueforti reveals a novel clavine alkaloid gene cluster.";
RL Appl. Microbiol. Biotechnol. 101:6111-6121(2017).
RN [3]
RP FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, COFACTOR, ACTIVE SITE, MUTAGENESIS
RP OF TYR-174, AND PATHWAY.
RX PubMed=28902217; DOI=10.1039/c7ob02095c;
RA Gerhards N., Li S.M.;
RT "A bifunctional old yellow enzyme from Penicillium roqueforti is involved
RT in ergot alkaloid biosynthesis.";
RL Org. Biomol. Chem. 15:8059-8071(2017).
CC -!- FUNCTION: Chanoclavine-I aldehyde reductase; part of the gene cluster
CC that mediates the biosynthesis of isofumigaclavines, fungal ergot
CC alkaloids (PubMed:28902217). The tryptophan dimethylallyltransferase
CC ifgA catalyzes the first step of ergot alkaloid biosynthesis by
CC condensing dimethylallyl diphosphate (DMAP) and tryptophan to form 4-
CC dimethylallyl-L-tryptophan (PubMed:28620689). The second step is
CC catalyzed by the methyltransferase ifgB that methylates 4-
CC dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine,
CC resulting in the formation of N-methyl-dimethylallyl-L-tryptophan
CC (PubMed:28620689). The catalase ifgD and the FAD-dependent
CC oxidoreductase ifgC then transform N-methyl-dimethylallyl-L-tryptophan
CC to chanoclavine-I which is further oxidized by ifgE in the presence of
CC NAD(+), resulting in the formation of chanoclavine-I aldehyde
CC (PubMed:28902217). The chanoclavine-I aldehyde reductases ifgG and/or
CC fgaOx3 reduce chanoclavine-I aldehyde to dihydrochanoclavine-I aldehyde
CC that spontaneously dehydrates to form 6,8-dimethyl-6,7-
CC didehydroergoline (PubMed:28620689, PubMed:28902217). The festuclavine
CC dehydrogenases ifgF1 and/or ifgF2 then catalyze the reduction of 6,8-
CC dimethyl-6,7-didehydroergoline to form festuclavine (PubMed:28620689).
CC Hydrolysis of festuclavine by a yet undetermined cytochrome P450
CC monooxygenase (called ifgH) then leads to the formation of
CC isofumigaclavine B which is in turn acetylated by ifgI to
CC isofumigaclavine A (PubMed:28620689). Penicillium roqueforti has
CC interestingly at least two sets of genes for the consumption of
CC chanoclavine-I aldehyde on three different loci, the OYEs ifgG/fgaOx3
CC and the festuclavine synthase homologs ifgF1/ifgF2 (PubMed:28620689,
CC PubMed:28902217). The reason for the duplication of these genes is
CC unclear, probably to ensure the conversion of chanoclavine-I aldehyde
CC by differential gene expression under various environmental conditions
CC (PubMed:28902217). {ECO:0000269|PubMed:28620689,
CC ECO:0000269|PubMed:28902217}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dihydrochanoclavine-I aldehyde + NADP(+) = chanoclavine-I
CC aldehyde + H(+) + NADPH; Xref=Rhea:RHEA:35947, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:65032,
CC ChEBI:CHEBI:71487; EC=1.3.1.100;
CC Evidence={ECO:0000269|PubMed:28902217};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:28902217};
CC -!- PATHWAY: Alkaloid biosynthesis; ergot alkaloid biosynthesis.
CC {ECO:0000269|PubMed:28902217}.
CC -!- SUBUNIT: Monomer (PubMed:28902217). {ECO:0000269|PubMed:28902217}.
CC -!- SIMILARITY: Belongs to the NADH:flavin oxidoreductase/NADH oxidase
CC family. {ECO:0000305}.
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DR EMBL; HG792017; CDM33403.1; -; Genomic_DNA.
DR AlphaFoldDB; W6Q9S9; -.
DR SMR; W6Q9S9; -.
DR STRING; 1365484.W6Q9S9; -.
DR EnsemblFungi; CDM33403; CDM33403; PROQFM164_S03g000127.
DR OrthoDB; 978998at2759; -.
DR UniPathway; UPA00327; -.
DR Proteomes; UP000030686; Unassembled WGS sequence.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0035835; P:indole alkaloid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR001155; OxRdtase_FMN_N.
DR InterPro; IPR045247; Oye-like.
DR PANTHER; PTHR22893; PTHR22893; 1.
DR Pfam; PF00724; Oxidored_FMN; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; Flavoprotein; FMN; NADP; Oxidoreductase.
FT CHAIN 1..369
FT /note="Chanoclavine-I aldehyde reductase fgaOx3"
FT /id="PRO_0000444542"
FT ACT_SITE 174
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:28902217"
FT BINDING 23..25
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 58
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 100
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 169
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 169
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT BINDING 172
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT BINDING 292
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 316..317
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q4WZ70"
FT BINDING 317
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT BINDING 344
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q02899"
FT MUTAGEN 174
FT /note="Y->F: Impairs the catalytic activity and formation
FT of festuclavine in vitro."
FT /evidence="ECO:0000269|PubMed:28902217"
SQ SEQUENCE 369 AA; 40053 MW; 745681DBD7B0C751 CRC64;
MTKLFTPLHV GRMELANRIA MAPMTRYRAS DNHVPLPIMK DYYAQRASVP GTLLITEATT
ISARAGGYAN APGIYNDAQI AAWKEVTDAV HAKGSYIYVQ LWAVGRPANP QLLQAEGGYD
LVSSSATAVS ADAPTPRALS ETEIYAWIAD YAQAARNAVA AGFDGVEIHA ANGYLIDQFT
QDICNTRTDA WGGSVQGRAR FALEVSRAVV EAVGADRTGI RFSPWSTFQG MRMKDPKPQF
EYLAVQTAKL GLAYVHLVES RIAGGADVDA TDRLDFFLRA YGKASPVIFA GGYDAESAVR
AVDVEYADYD AIVGIGRPFI SNPDLPFRVQ NGIPFVPYDR ATFYVPKDPK GYTDYAFSAE
FQKAIEAAA
