NVFM_ASPN1
ID NVFM_ASPN1 Reviewed; 327 AA.
AC A0A2I1BSW0;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2018, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Asnovolin J 5',6'-dehydrogenase nvfM {ECO:0000303|PubMed:29968715};
DE EC=1.3.99.- {ECO:0000269|PubMed:29968715};
DE AltName: Full=Novofumigatonin biosynthesis cluster protein M {ECO:0000303|PubMed:29968715};
GN Name=nvfM {ECO:0000303|PubMed:29968715}; ORFNames=P174DRAFT_436150;
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: Asnovolin J 5',6'-dehydrogenase; 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 + asnovolin K = A + asnovolin A; Xref=Rhea:RHEA:67064,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:17499, ChEBI:CHEBI:156459,
CC ChEBI:CHEBI:167685; Evidence={ECO:0000269|PubMed:29968715};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67065;
CC Evidence={ECO:0000269|PubMed:29968715};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + chermesin D methyl ester = A + asnovolin J;
CC Xref=Rhea:RHEA:67068, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:167683, ChEBI:CHEBI:167691;
CC Evidence={ECO:0000269|PubMed:29968715};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67069;
CC Evidence={ECO:0000269|PubMed:29968715};
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 and asnovolin A, but accumulates asnovolin I and
CC asnovolin K. {ECO:0000269|PubMed:29968715}.
CC -!- SIMILARITY: Belongs to the NmrA-type oxidoreductase family.
CC {ECO:0000305}.
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DR EMBL; MSZS01000014; PKX88475.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2I1BSW0; -.
DR SMR; A0A2I1BSW0; -.
DR VEuPathDB; FungiDB:P174DRAFT_436150; -.
DR OrthoDB; 1054772at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000234474; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR008030; NmrA-like.
DR Pfam; PF05368; NmrA; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Membrane; NADP; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..327
FT /note="Asnovolin J 5',6'-dehydrogenase nvfM"
FT /id="PRO_0000453088"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 130
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9LD14"
FT BINDING 13..19
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9LD14"
FT BINDING 47
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9LD14"
SQ SEQUENCE 327 AA; 36157 MW; C1816D1093BF03A2 CRC64;
MAITDTINVA IVGASGVTGG SIVNGLLALT GLTVKITALT RPESLNKPAN IQLKERGVQV
VAANLRGPLE KLVDLLSSID VVISAIYWGS LDDEIPLANA AKAAGVKRFV QSAYNIPAAA
RGVTHLRDKK EVILSHIQQL RLPYTYIDVG WWYHVVLPRV ASGRTEHALP FGMPDLPIAL
DGNIPSGLTH IRDIGRYIAR IILDPRTVNK KVFVYNELYT QNQLCDLVER LTGEMPQRRY
ISEKCVQSWL QEALDELERN PSSDIALGVV SLREVFLASN VHGTNTPEYA KYLGYLDGKE
LYPDFTFLTY EDYVEEVLDG MHSQTVA
