NVFF_ASPN1
ID NVFF_ASPN1 Reviewed; 298 AA.
AC A0A2I1BSZ6;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2018, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Fe(II)/2-oxoglutarate-dependent dioxygenase nvfF {ECO:0000303|PubMed:29968715};
DE EC=1.14.11.- {ECO:0000269|PubMed:29968715};
DE AltName: Full=Novofumigatoninbiosynthesis cluster protein F {ECO:0000303|PubMed:29968715};
GN Name=nvfF {ECO:0000303|PubMed:29968715}; ORFNames=P174DRAFT_425993;
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 + fumigatonoid C + O2 = CO2 + H2O +
CC novofumigatonin + succinate; Xref=Rhea:RHEA:67104, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:156460, ChEBI:CHEBI:167689;
CC Evidence={ECO:0000269|PubMed:29968715};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67105;
CC Evidence={ECO:0000269|PubMed:29968715};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q4WAW9};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:29968715}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q4WAW9}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC novofumigatonin, but accumulates asnovolin G and asnovolin A.
CC {ECO:0000269|PubMed:29968715}.
CC -!- SIMILARITY: Belongs to the PhyH family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; MSZS01000014; PKX88482.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2I1BSZ6; -.
DR SMR; A0A2I1BSZ6; -.
DR VEuPathDB; FungiDB:P174DRAFT_425993; -.
DR OrthoDB; 623398at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000234474; Unassembled WGS sequence.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..298
FT /note="Fe(II)/2-oxoglutarate-dependent dioxygenase nvfF"
FT /id="PRO_0000453081"
FT BINDING 137
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 139
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
FT BINDING 212
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:O14832"
SQ SEQUENCE 298 AA; 33265 MW; 59066070B2A921FA CRC64;
MTVSTPSKPH ICRFPPGADP DVINQAFRED GVVILEGFLT PAQVDKVNCE MKPHLAKVRG
GNMRYGPMDT SLETTLEPER RRIHNLAGLS ETFRQDILNH PLMHELSRRV FSEFGDYWQY
AGSVIDCAPG TPDQFLHRDQ PAQKLFNVGP DAPEGFINFL TALTDFTKTN GATRFVWGSH
RDWIDKSDEN HPIVVAEVKA GDSLFFSGKI VHGGSFNGTN DTYRSSVALP IVPCIMTPYE
ANIHIPRSTV ETMTPLAQRM IGWRSACLPD PYAIGTWTLN MNELGEQMGL KSKGYLEN
