TRAG_PENCR
ID TRAG_PENCR Reviewed; 364 AA.
AC A0A481WQL4;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 7.
DE RecName: Full=Trans-enoyl reductase traG {ECO:0000303|PubMed:30811183};
DE EC=1.-.-.- {ECO:0000305|PubMed:30811183};
DE AltName: Full=Terrestric acid biosynthesis cluster protein G {ECO:0000303|PubMed:30811183};
GN Name=traG {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], AND FUNCTION.
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: Trans-enoyl reductase; part of the tra gene cluster that
CC produces terrestric acid (PubMed:30811183). The clavatol biosynthesis
CC cluster cla and the terrestric acid cluster tra are both involved in
CC the production of peniphenones and penilactones (PubMed:30811183). The
CC non-reducing PKS claF is responsible for the formation of clavatol from
CC successive condensations of 3 malonyl-CoA units, presumably with a
CC simple acetyl-CoA starter unit, and 2 methylation steps
CC (PubMed:30811183). The esterase claE probably collaborates with claF by
CC catalyzing the hydrolysis of ACP-bound acyl intermediates to free the
CC ACP from stalled intermediates (By similarity). The clavatol oxidase
CC claD then converts clavatol to hydroxyclavatol (PubMed:30811183).
CC Spontaneous dehydration of hydroxyclavatol leads to the accumulation of
CC the highly active ortho-quinone methide (PubMed:30811183,
CC PubMed:31860310). On the other hand, the PKS-NRPS hybrid traA is
CC involved in the formation of crustosic acid, with the help of traB and
CC traD (PubMed:30811183). The polyketide synthase module (PKS) of traA is
CC responsible for the synthesis of the polyketide backbone via the
CC condensation of an acetyl-CoA starter unit with 3 malonyl-CoA units
CC (PubMed:30811183). The downstream nonribosomal peptide synthetase
CC (NRPS) module then amidates the carboxyl end of the polyketide with L-
CC malic acid (PubMed:30811183). Because traA lacks a designated
CC enoylreductase (ER) domain, the required activity is provided the enoyl
CC reductase traG (By similarity). Crustosic acid undergoes
CC decarboxylation and isomerization to the terrestric acid, catalyzed by
CC the 2-oxoglutarate-dependent dioxygenase traH (PubMed:30811183). Both
CC acids are further converted to the 2 gamma-butyrolactones (R)-5-
CC methyltetronic acid and (S)-5-carboxylmethyltetronic acid, with
CC involvement of the cytochrome P450 monooxygenase claJ
CC (PubMed:30811183). Spontaneous addition of the methide to these gamma-
CC butyrolactones leads to peniphenone D and penilactone D, which undergo
CC again stereospecific attacking by methide to give penilactones A and B
CC (PubMed:30811183, PubMed:31860310). {ECO:0000250|UniProtKB:A0A0E0RXA7,
CC ECO:0000250|UniProtKB:A0A161CKG1, ECO:0000269|PubMed:30811183,
CC ECO:0000269|PubMed:31860310}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000250|UniProtKB:A0A0E0RXA7}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; MK360919; QBK15055.1; -; Genomic_DNA.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW NADP; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..364
FT /note="Trans-enoyl reductase traG"
FT /id="PRO_0000455062"
FT BINDING 51..54
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 136..143
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 176..179
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 199..202
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 217
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 264..265
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 286..290
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 355..356
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 364 AA; 38812 MW; 985EF606B9A99653 CRC64;
MPSATPILPR QQTAIVAEAA GKLRIQHNVT VPSPGPMVAI VKTAAVAINP VDAKMLDYSP
VPGAVHGYDF AGTIVSMGPN TPAHLRIGDR VAGWVHGMNA VEPNVGAFAE YVASPADLIL
RIPDEMSFND AASIGLGLFT AGLGLFHELK VPGSLSDPDG LEIAEDERFV LVAGGSTATG
TRAIQLLRLA GLRPIATCSK ANMDLVHRFG AEHAFDYSDP ECAAEIRRYT GGTLAYALDC
VAMADTTQLC YNAMGRAGGR YVTLEPFRSA IAETRPLTIE PSWLLALTVF GRKVDIDGEY
SRDARPDDHK FAVELTVSVQ ALLDQGKFDT HPIKVMNGGW DGVKEGVDTI RTQAMSGQKL
VYPV
