TRAH_PENCR
ID TRAH_PENCR Reviewed; 327 AA.
AC A0A481WQ18;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=2-oxoglutarate-dependent dioxygenase traH {ECO:0000303|PubMed:30811183};
DE EC=1.14.-.- {ECO:0000305|PubMed:30811183};
DE AltName: Full=Terrestric acid biosynthesis cluster protein H {ECO:0000303|PubMed:30811183};
GN Name=traH {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: 2-oxoglutarate-dependent dioxygenase; part of the tra gene
CC cluster that produces terrestric acid (PubMed:30811183). The clavatol
CC biosynthesis cluster cla and the terrestric acid cluster tra are both
CC involved in the production of peniphenones and penilactones
CC (PubMed:30811183). The non-reducing PKS claF is responsible for the
CC formation of clavatol from successive condensations of 3 malonyl-CoA
CC units, presumably with a simple acetyl-CoA starter unit, and 2
CC methylation steps (PubMed:30811183). The esterase claE probably
CC collaborates with claF by catalyzing the hydrolysis of ACP-bound acyl
CC intermediates to free the ACP from stalled intermediates (By
CC similarity). The clavatol oxidase claD then converts clavatol to
CC hydroxyclavatol (PubMed:30811183). Spontaneous dehydration of
CC hydroxyclavatol leads to the accumulation of the highly active ortho-
CC quinone methide (PubMed:30811183, PubMed:31860310). On the other hand,
CC the PKS-NRPS hybrid traA is involved in the formation of crustosic
CC acid, with the help of traB and traD (PubMed:30811183). The polyketide
CC synthase module (PKS) of traA is responsible for the synthesis of the
CC polyketide backbone via the condensation of an acetyl-CoA starter unit
CC with 3 malonyl-CoA units (PubMed:30811183). The downstream nonribosomal
CC peptide synthetase (NRPS) module then amidates the carboxyl end of the
CC polyketide with L-malic acid (PubMed:30811183). Because traA lacks a
CC designated enoylreductase (ER) domain, the required activity is
CC provided the enoyl reductase traG (By similarity). Crustosic acid
CC undergoes decarboxylation and isomerization to the terrestric acid,
CC catalyzed by the 2-oxoglutarate-dependent dioxygenase traH
CC (PubMed:30811183). Both acids are further converted to the 2 gamma-
CC 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=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30811183}.
CC -!- DISRUPTION PHENOTYPE: Abolished the production of penilactone A,
CC peniphenone D and terrestric acid. {ECO:0000269|PubMed:30811183}.
CC -!- SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase
CC family. {ECO:0000305}.
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DR EMBL; MK360919; QBK15056.1; -; Genomic_DNA.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.330; -; 1.
DR InterPro; IPR026992; DIOX_N.
DR InterPro; IPR044861; IPNS-like_FE2OG_OXY.
DR InterPro; IPR027443; IPNS-like_sf.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR Pfam; PF14226; DIOX_N; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 3: Inferred from homology;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT CHAIN 1..327
FT /note="2-oxoglutarate-dependent dioxygenase traH"
FT /id="PRO_0000455069"
FT DOMAIN 183..290
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 211
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 213
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 270
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 280
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
SQ SEQUENCE 327 AA; 37491 MW; B1CBB336F484E0A6 CRC64;
MSVDAAVVKN EDKYIPTIDL RDYFDAYSEE KRAKVIEQVR KACLEHGFFQ VEGHGVPVES
QRRMFAACKA LFDLPLEKKR RISLYKYSWR RGYEGPGEQQ ANDPHHGDFE RDAKEGFFVG
KELPLDQVDF GKGPNVWPPD LAENDFHRPV MEYYEHARKV GFKVMELLAV SLGHPPSILK
DFTTDAAMFL KLLRYPAHTW TDTRKFGSGQ HTDYGGITIL LQDPGQDGLE VWHEATQQWV
ELPALEDKFV INLGDMVQRW TGGKYKSTLH RVINKTGGER YAVPAFWHGD LDAKNPLDPN
DTSDETVLEF IKKKFYKGYG LTDDTSL
