NVFI_ASPN1
ID NVFI_ASPN1 Reviewed; 278 AA.
AC A0A2I1BSX0;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 2.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Fe(II)/2-oxoglutarate-dependent dioxygenase nvfI {ECO:0000303|PubMed:29968715};
DE EC=1.14.11.- {ECO:0000269|PubMed:29968715};
DE AltName: Full=Fumigatonoid A synthase nvfI {ECO:0000303|PubMed:29968715};
DE AltName: Full=Novofumigatonin biosynthesis cluster protein I {ECO:0000303|PubMed:29968715};
GN Name=nvfI {ECO:0000303|PubMed:29968715}; ORFNames=P174DRAFT_436154;
OS Aspergillus novofumigatus (strain IBT 16806).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=1392255;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=IBT 16806;
RX PubMed=29317534; DOI=10.1073/pnas.1715954115;
RA Kjaerboelling I., Vesth T.C., Frisvad J.C., Nybo J.L., Theobald S., Kuo A.,
RA Bowyer P., Matsuda Y., Mondo S., Lyhne E.K., Kogle M.E., Clum A.,
RA Lipzen A., Salamov A., Ngan C.Y., Daum C., Chiniquy J., Barry K.,
RA LaButti K., Haridas S., Simmons B.A., Magnuson J.K., Mortensen U.H.,
RA Larsen T.O., Grigoriev I.V., Baker S.E., Andersen M.R.;
RT "Linking secondary metabolites to gene clusters through genome sequencing
RT of six diverse Aspergillus species.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E753-E761(2018).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=29968715; DOI=10.1038/s41467-018-04983-2;
RA Matsuda Y., Bai T., Phippen C.B.W., Noedvig C.S., Kjaerboelling I.,
RA Vesth T.C., Andersen M.R., Mortensen U.H., Gotfredsen C.H., Abe I.,
RA Larsen T.O.;
RT "Novofumigatonin biosynthesis involves a non-heme iron-dependent
RT endoperoxide isomerase for orthoester formation.";
RL Nat. Commun. 9:2587-2587(2018).
CC -!- FUNCTION: Fe(II)/2-oxoglutarate-dependent dioxygenase; part of the gene
CC cluster that mediates the biosynthesis of novofumigatonin, a heavily
CC oxygenated meroterpenoid containing a unique orthoester moiety
CC (PubMed:29968715). The first step of the pathway is the synthesis of
CC 3,5-dimethylorsellinic acid (DMOA) by the polyketide synthase nvfA via
CC condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units
CC and 2 methylations (PubMed:29968715). DMOA is then converted to
CC farnesyl-DMOA by the farnesyltransferase nvfB (PubMed:29968715).
CC Epoxydation by FAD-dependent monooxygenase nvfK, followed by a
CC protonation-initiated cyclization catalyzed by the terpene cyclase nvfL
CC leads to the production of asnavolin H (PubMed:29968715). The short
CC chain dehydrogenase nvfC then as a 3-OH dehydrogenase of asnovolin H to
CC yield chemesin D (PubMed:29968715). There are two branches to
CC synthesize asnovolin A from chemesin D (PubMed:29968715). In one
CC branch, chemesin D undergoes Baeyer-Villiger oxidation by nvfH,
CC methylation by nvfJ, and enoyl reduction by the nvfM D enoylreductase
CC that reduces the double bond between C-5'and C-6', to form respectively
CC asnovolin I, asnovolin K, and asnovolin A (PubMed:29968715). In the
CC other branch, the methylation precedes the Baeyer-Villiger oxidation
CC and the enoyl reduction to yield asnovolin A via the asnovolin J
CC intermediate (PubMed:29968715). Asnovolin A is further converted to
CC fumigatonoid A by the Fe(II)/2-oxoglutarate-dependent dioxygenase nvfI
CC that catalyzes an endoperoxidation reaction (PubMed:29968715). The
CC alpha/beta hydrolase nvfD then acts as an epimerase that converts
CC fumigatonoid A to its C-5' epimer, which then undergoes spontaneous or
CC nvfD-catalyzed lactonization (PubMed:29968715). The following step
CC utilizes the ketoreductase nvfG to produce fumigatonoid B
CC (PubMed:29968715). The dioxygenase nvfE further converts fumigatonoid B
CC into fumigatonoid C (PubMed:29968715). Finally the Fe(II)/2-
CC oxoglutarate-dependent dioxygenase nvfF catalyzes two rounds of
CC oxidation to transform fumigatonoid C into the end product,
CC novofumigatonin A (PubMed:29968715). {ECO:0000269|PubMed:29968715}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + asnovolin A + 2 O2 = CO2 + fumigatonoid A +
CC succinate; Xref=Rhea:RHEA:67096, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:156459, ChEBI:CHEBI:167687;
CC Evidence={ECO:0000269|PubMed:29968715};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67097;
CC Evidence={ECO:0000269|PubMed:29968715};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:29968715}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC novofumigatonin, but accumulates asnovolin A.
CC {ECO:0000269|PubMed:29968715}.
CC -!- SIMILARITY: Belongs to the asaB hydroxylase/desaturase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=PKX88479.1; Type=Erroneous gene model prediction; Evidence={ECO:0000269|PubMed:29968715};
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DR EMBL; MSZS01000014; PKX88479.1; ALT_SEQ; Genomic_DNA.
DR PDB; 7DE2; X-ray; 1.90 A; A/B=1-278.
DR PDB; 7EMZ; X-ray; 2.30 A; A/B=1-278.
DR PDB; 7ENB; X-ray; 2.30 A; A/B=1-278.
DR PDBsum; 7DE2; -.
DR PDBsum; 7EMZ; -.
DR PDBsum; 7ENB; -.
DR AlphaFoldDB; A0A2I1BSX0; -.
DR SMR; A0A2I1BSX0; -.
DR VEuPathDB; FungiDB:P174DRAFT_436154; -.
DR OrthoDB; 867824at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000234474; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR044053; AsaB-like.
DR PANTHER; PTHR34598; PTHR34598; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Oxidoreductase; Reference proteome.
FT CHAIN 1..278
FT /note="Fe(II)/2-oxoglutarate-dependent dioxygenase nvfI"
FT /id="PRO_0000453084"
FT STRAND 7..15
FT /evidence="ECO:0007829|PDB:7DE2"
FT TURN 17..20
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 25..30
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 43..51
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 53..58
FT /evidence="ECO:0007829|PDB:7DE2"
FT TURN 61..64
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 75..82
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 86..90
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 92..105
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 108..119
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 140..151
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 155..158
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 163..175
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 181..184
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:7DE2"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 194..204
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 221..223
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 231..241
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:7DE2"
FT STRAND 266..276
FT /evidence="ECO:0007829|PDB:7DE2"
SQ SEQUENCE 278 AA; 31742 MW; 413FD8616642AF02 CRC64;
MVGSRTWCES EMLFVQPDAG TKEELYYRVT PKPGQTQANF NWTPHKVRFH DARPQRDSFD
LNTHGFTFVE DAISPQLIER IRADDTAAVE GDYFASVAAL VKRVTGADHV VCFSPYTRKE
NSEKGIFGQP ARTVHCDHTP AAAIELTHKL CGEDAVRLLQ SRFRAFSVWR PLVEPVLDWP
LAVVDGRTIA PDDLHPVHWL RYEKKDTEPP FQLSFSETQK WYYLSRQRSD EVSIVKNYDS
EVVPSPRSAH CAFKHPFVPK DAPPRESIDV RCLVFGGR
