NVFJ_ASPN1
ID NVFJ_ASPN1 Reviewed; 278 AA.
AC A0A2I1BSV7;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2018, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Asnovolin E/Chermesin D methyltransferase nvfJ {ECO:0000303|PubMed:29968715};
DE EC=2.1.1.- {ECO:0000269|PubMed:29968715};
DE AltName: Full=Novofumigatonin biosynthesis cluster protein J {ECO:0000303|PubMed:29968715};
GN Name=nvfJ {ECO:0000303|PubMed:29968715}; ORFNames=P174DRAFT_425989;
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: Methyltransferase; part of the gene cluster that mediates the
CC biosynthesis of novofumigatonin, a heavily oxygenated meroterpenoid
CC containing a unique orthoester moiety (PubMed:29968715). The first step
CC of the pathway is the synthesis of 3,5-dimethylorsellinic acid (DMOA)
CC by the polyketide synthase nvfA via condensation of one acetyl-CoA
CC starter unit with 3 malonyl-CoA units and 2 methylations
CC (PubMed:29968715). DMOA is then converted to farnesyl-DMOA by the
CC farnesyltransferase nvfB (PubMed:29968715). Epoxydation by FAD-
CC dependent monooxygenase nvfK, followed by a protonation-initiated
CC cyclization catalyzed by the terpene cyclase nvfL leads to the
CC production of asnavolin H (PubMed:29968715). The short chain
CC dehydrogenase nvfC then as a 3-OH dehydrogenase of asnovolin H to yield
CC chemesin D (PubMed:29968715). There are two branches to synthesize
CC asnovolin A from chemesin D (PubMed:29968715). In one branch, chemesin
CC D undergoes Baeyer-Villiger oxidation by nvfH, methylation by nvfJ, and
CC enoyl reduction by the nvfM D enoylreductase that reduces the double
CC bond between C-5'and C-6', to form respectively asnovolin I, asnovolin
CC K, and asnovolin A (PubMed:29968715). In the other branch, the
CC methylation precedes the Baeyer-Villiger oxidation and the enoyl
CC reduction to yield asnovolin A via the asnovolin J intermediate
CC (PubMed:29968715). Asnovolin A is further converted to fumigatonoid A
CC by the Fe(II)/2-oxoglutarate-dependent dioxygenase nvfI that catalyzes
CC an endoperoxidation reaction (PubMed:29968715). The alpha/beta
CC hydrolase nvfD then acts as an epimerase that converts fumigatonoid A
CC to its C-5' epimer, which then undergoes spontaneous or nvfD-catalyzed
CC lactonization (PubMed:29968715). The following step utilizes the
CC ketoreductase nvfG to produce fumigatonoid B (PubMed:29968715). The
CC dioxygenase nvfE further converts fumigatonoid B into fumigatonoid C
CC (PubMed:29968715). Finally the Fe(II)/2-oxoglutarate-dependent
CC dioxygenase nvfF catalyzes two rounds of oxidation to transform
CC fumigatonoid C into the end product, novofumigatonin A
CC (PubMed:29968715). {ECO:0000269|PubMed:29968715}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chermesin D + S-adenosyl-L-methionine = chermesin D methyl
CC ester + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:67056,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156464,
CC ChEBI:CHEBI:167691; Evidence={ECO:0000269|PubMed:29968715};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67057;
CC Evidence={ECO:0000269|PubMed:29968715};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=asnovolin I + S-adenosyl-L-methionine = asnovolin K + S-
CC adenosyl-L-homocysteine; Xref=Rhea:RHEA:67060, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:167684, ChEBI:CHEBI:167685;
CC Evidence={ECO:0000269|PubMed:29968715};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67061;
CC Evidence={ECO:0000269|PubMed:29968715};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:29968715}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q3J7D1}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of both
CC novofumigatonin and asnovolin A, but accumulates the tetracyclic
CC intermediate asnovolin I. {ECO:0000269|PubMed:29968715}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. {ECO:0000305}.
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DR EMBL; MSZS01000014; PKX88478.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2I1BSV7; -.
DR SMR; A0A2I1BSV7; -.
DR STRING; 1392255.A0A2I1BSV7; -.
DR VEuPathDB; FungiDB:P174DRAFT_425989; -.
DR OrthoDB; 1471762at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000234474; Unassembled WGS sequence.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..278
FT /note="Asnovolin E/Chermesin D methyltransferase nvfJ"
FT /id="PRO_0000453085"
FT BINDING 125..126
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q3J7D1"
FT BINDING 152..153
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q3J7D1"
FT BINDING 153..154
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q3J7D1"
SQ SEQUENCE 278 AA; 31863 MW; BFF80B9464199DE2 CRC64;
MTVETITPQT PVSLPKTAVI CNDFKLDRVN EPARSILEKY SKIPSREILE HVRKIRDEAF
AEFPYPCIGR FSFLDLSISQ SPKYPEILHR VVNGEKFLDL GCAFGQELRQ LVYDGAPSDN
LYGSDLHNGL MHLGYDLFRD VSTLKSRFIA TNILEGNSDL ISQLSGQMNI IYSSLFFHLF
DWDQSLVIAK HVLRLLSLQP GSMITGRFVA YRDWNFAKEK LGSTLRFYFD LSSWTQLWKQ
VEVDTGSKLN IEHWEQSDNM LTDNGIGGYM LCFAITRQ
