NVFH_ASPN1
ID NVFH_ASPN1 Reviewed; 661 AA.
AC A0A2I1BSU0;
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=Chermesin D/asnovolin J monooxidase nvfH {ECO:0000303|PubMed:29968715};
DE EC=1.14.-.- {ECO:0000269|PubMed:29968715};
DE AltName: Full=Baeyer-Villiger monooxygenase nvfH {ECO:0000303|PubMed:29968715};
DE AltName: Full=Novofumigatonin biosynthesis cluster protein H {ECO:0000303|PubMed:29968715};
GN Name=nvfF {ECO:0000303|PubMed:29968715}; ORFNames=P174DRAFT_425991;
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: Chermesin D/asnovolin J monooxidase; part of the gene cluster
CC that mediates the biosynthesis of novofumigatonin, a heavily oxygenated
CC meroterpenoid containing a unique orthoester moiety (PubMed:29968715).
CC The first step of the pathway is the synthesis of 3,5-
CC 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=AH2 + chermesin D + O2 = A + asnovolin I + H2O;
CC Xref=Rhea:RHEA:67048, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:156464,
CC ChEBI:CHEBI:167684; Evidence={ECO:0000269|PubMed:29968715};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67049;
CC Evidence={ECO:0000269|PubMed:29968715};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + asnovolin J + O2 = A + asnovolin A + H2O;
CC Xref=Rhea:RHEA:67052, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:156459,
CC ChEBI:CHEBI:167683; Evidence={ECO:0000269|PubMed:29968715};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67053;
CC Evidence={ECO:0000269|PubMed:29968715};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:H3JQW0};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:H3JQW0};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:29968715}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC novofumigatonin, but accumulates asnovolin J.
CC {ECO:0000269|PubMed:29968715}.
CC -!- SIMILARITY: Belongs to the FAD-binding monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; MSZS01000014; PKX88480.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2I1BSU0; -.
DR SMR; A0A2I1BSU0; -.
DR STRING; 1392255.A0A2I1BSU0; -.
DR VEuPathDB; FungiDB:P174DRAFT_425991; -.
DR OrthoDB; 405736at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000234474; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR SUPFAM; SSF51905; SSF51905; 2.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Monooxygenase; NADP;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..661
FT /note="Chermesin D/asnovolin J monooxidase nvfH"
FT /id="PRO_0000453083"
FT TRANSMEM 89..111
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 128..131
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 138..140
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 140..141
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 146
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 286..292
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 309..310
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT SITE 428
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT CARBOHYD 12
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 538
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 661 AA; 74453 MW; D3B4F443BC8E850B CRC64;
MDVTEIAEQT LNTSCLSPAC QQQDYAEIEK RYEAERHQQL QTRGKIPDVN IRTNTRFEQF
SKDPWLDDSN KRQQIQYHQR RHNGKHHKVL IIGAGYGGLL FAVRIIQTGA FTADDILMVD
TSGGFGGTWY WNRYPGLMCD VESYIYMPLL EETGYMPRAK YASGPELRVH AERIADTWKL
SNRAMFGVTV KSLDWDEVGK HWSARGLVLD YEKDQSKKAS LHLSADFVML ASGIFASPKI
PDFTSILEYH GHMFHTSRWD YGCTGGSPEN PKLCKLGDKK VGIIGTGATA IQVVPHLAQY
SKELHVFQRT PSAVDKRDNH PTDPVWWNKM LQSEGPGWQK RRMENFNAFT GNEQPQPAVD
MIADGWTSMP SFSIIGGSPE SNATDYLHRM KAFDFPRQER IRARVRETVH NKEVAEALSP
WYPGWCKRPC FHDHYLAAFN RPNVRLIDVR QSGIDHFTPK GLVADGREHE IDVFVFSTGY
TTSRSSPGGR ADIAITGRNG LTMEHKWQNG LATLHGVITR DFPNLFFPGP SQAGTCLNHT
YTLDQLATHV AYIISKTLIK IGAADAGYSP RVVIEPTKEA EEDWAVQVLA RAATHGALSQ
CTPGYYNRDG MASAMKSLSM EDKMKLGRMV SWGEGIGSYM DQIVNWRGQG ELRGLEIHCV
D
