TRAD_PENCR
ID TRAD_PENCR Reviewed; 267 AA.
AC A0A481WNM5;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 5.
DE RecName: Full=Ribosyldihydronicotinamide dehydrogenase-like protein traD {ECO:0000303|PubMed:30811183};
DE EC=1.10.-.- {ECO:0000305|PubMed:30811183};
DE AltName: Full=Terrestric acid biosynthesis cluster protein D {ECO:0000303|PubMed:30811183};
GN Name=traD {ECO:0000303|PubMed:30811183};
OS Penicillium crustosum (Blue mold fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=36656;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=PRB-2;
RX PubMed=30811183; DOI=10.1021/jacs.9b00110;
RA Fan J., Liao G., Kindinger F., Ludwig-Radtke L., Yin W.B., Li S.M.;
RT "Peniphenone and penilactone formation in Penicillium crustosum via 1,4-
RT Michael additions of ortho-quinone methide from hydroxyclavatol to gamma-
RT butyrolactones from Crustosic Acid.";
RL J. Am. Chem. Soc. 141:4225-4229(2019).
RN [2]
RP FUNCTION.
RX PubMed=31860310; DOI=10.1021/acs.joc.9b02971;
RA Liao G., Fan J., Ludwig-Radtke L., Backhaus K., Li S.M.;
RT "Increasing Structural Diversity of Natural Products by Michael Addition
RT with ortho-Quinone Methide as the Acceptor.";
RL J. Org. Chem. 85:1298-1307(2020).
CC -!- FUNCTION: Ribosyldihydronicotinamide dehydrogenase-like protein; part
CC of the tra gene cluster that produces terrestric acid
CC (PubMed:30811183). The clavatol biosynthesis cluster cla and the
CC terrestric acid cluster tra are both involved in the production of
CC peniphenones and penilactones (PubMed:30811183). The non-reducing PKS
CC claF is responsible for the formation of clavatol from successive
CC condensations of 3 malonyl-CoA units, presumably with a simple acetyl-
CC CoA starter unit, and 2 methylation steps (PubMed:30811183). The
CC esterase claE probably collaborates with claF by catalyzing the
CC hydrolysis of ACP-bound acyl intermediates to free the ACP from stalled
CC intermediates (By similarity). The clavatol oxidase claD then converts
CC clavatol to hydroxyclavatol (PubMed:30811183). Spontaneous dehydration
CC of hydroxyclavatol leads to the accumulation of the highly active
CC ortho-quinone methide (PubMed:30811183, PubMed:31860310). On the other
CC hand, the PKS-NRPS hybrid traA is involved in the formation of
CC crustosic acid, with the help of traB and traD (PubMed:30811183). The
CC polyketide synthase module (PKS) of traA is responsible for the
CC synthesis of the polyketide backbone via the condensation of an acetyl-
CC CoA starter unit with 3 malonyl-CoA units (PubMed:30811183). The
CC downstream nonribosomal peptide synthetase (NRPS) module then amidates
CC the carboxyl end of the polyketide with L-malic acid (PubMed:30811183).
CC Because traA lacks a designated enoylreductase (ER) domain, the
CC required activity is provided the enoyl reductase traG (By similarity).
CC Crustosic acid undergoes decarboxylation and isomerization to the
CC terrestric acid, catalyzed by the 2-oxoglutarate-dependent dioxygenase
CC traH (PubMed:30811183). Both acids are further converted to the 2
CC gamma-butyrolactones (R)-5-methyltetronic acid and (S)-5-
CC carboxylmethyltetronic acid, with involvement of the cytochrome P450
CC monooxygenase claJ (PubMed:30811183). Spontaneous addition of the
CC methide to these gamma-butyrolactones leads to peniphenone D and
CC penilactone D, which undergo again stereospecific attacking by methide
CC to give penilactones A and B (PubMed:30811183, PubMed:31860310).
CC {ECO:0000250|UniProtKB:A0A0E0RXA7, ECO:0000250|UniProtKB:A0A161CKG1,
CC ECO:0000269|PubMed:30811183, ECO:0000269|PubMed:31860310}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P15559};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30811183}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P15559}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC peniphenone D, penilactone D, penilactone A and penilactone B, as well
CC as of crustosic acid and terrestric acid.
CC {ECO:0000269|PubMed:30811183}.
CC -!- SIMILARITY: Belongs to the NAD(P)H dehydrogenase (quinone) family.
CC {ECO:0000305}.
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DR EMBL; MK360919; QBK15052.1; -; Genomic_DNA.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.360; -; 1.
DR InterPro; IPR003680; Flavodoxin_fold.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR Pfam; PF02525; Flavodoxin_2; 1.
DR SUPFAM; SSF52218; SSF52218; 1.
PE 3: Inferred from homology;
KW FAD; Flavoprotein; NAD; NADP; Oxidoreductase.
FT CHAIN 1..267
FT /note="Ribosyldihydronicotinamide dehydrogenase-like
FT protein traD"
FT /id="PRO_0000455063"
FT BINDING 9
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 15..16
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 100..103
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 122..124
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 152..155
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
FT BINDING 160
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P15559"
SQ SEQUENCE 267 AA; 30692 MW; 9498BF5873C5875D CRC64;
MKVLIIFAHP EPQSLNGALH RVAVEELEEQ GHHVQVSDLY KMKWKSEVDR EDFPNFPKDQ
RLDLWTASAE AYAENSLTQD VLDEQAKLRW ADFVIFHFPL WWFTMPAILK GWVDRVYTYG
FGHGLGEHSD KRWGDRYGEG TLTGKRAMLI VTLGGWKEHY SARGISGPIE DVLFPINHGI
LFYPGFEVLP PFVAFRVHKT SFDEMASTLR KRMREIEFTK PIPYRNQNDG EYSIPTLTLH
ESHGGDLASG FGLHTRTEVE TTDVKEA
