ID   PHM4_PYRSX              Reviewed;         362 AA.
AC   A0A2Z5XAK4;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2018, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=Trans-enoyl reductase phm4 {ECO:0000303|PubMed:29972614};
DE            Short=ER phm4 {ECO:0000303|PubMed:29972614};
DE            EC=1.-.-.- {ECO:0000269|PubMed:29972614};
DE   AltName: Full=Phomasetin biosynthesis cluster protein 4 {ECO:0000303|PubMed:29972614};
GN   Name=phm4 {ECO:0000303|PubMed:29972614};
OS   Pyrenochaetopsis sp.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC   Pleosporomycetidae; Pleosporales; Pleosporineae; Pyrenochaetopsidaceae;
OC   Pyrenochaetopsis; unclassified Pyrenochaetopsis.
OX   NCBI_TaxID=1756125;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, DISRUPTION
RP   PHENOTYPE, AND PATHWAY.
RC   STRAIN=RK10-F058;
RX   PubMed=29972614; DOI=10.1002/anie.201805050;
RA   Kato N., Nogawa T., Takita R., Kinugasa K., Kanai M., Uchiyama M.,
RA   Osada H., Takahashi S.;
RT   "Control of the stereochemical course of [4+2] cycloaddition during trans-
RT   decalin formation by Fsa2-family enzymes.";
RL   Angew. Chem. Int. Ed. 57:9754-9758(2018).
RN   [2]
RP   FUNCTION.
RX   PubMed=34121297; DOI=10.1002/anie.202106186;
RA   Fujiyama K., Kato N., Re S., Kinugasa K., Watanabe K., Takita R.,
RA   Nogawa T., Hino T., Osada H., Sugita Y., Takahashi S., Nagano S.;
RT   "Molecular basis for two stereoselective Diels-Alderases that produce
RT   decalin skeletons*.";
RL   Angew. Chem. Int. Ed. 60:22401-22410(2021).
CC   -!- FUNCTION: Trans-enoyl reductase; part of the gene cluster that mediates
CC       the biosynthesis of the trans-fused decalin-containing tetramic acid
CC       phomasetin, the stereochemical opposite of the HIV-1 integrase
CC       inhibitor equisetin (PubMed:29972614). The PKS module of phm1 together
CC       with the enoylreductase phm4 catalyze the formation of the polyketide
CC       unit which is then conjugated to L-serine by the condensation domain of
CC       the phm1 NRPS module (PubMed:29972614). Activity of the Dieckmann
CC       cyclase domain (RED) of phm1 results in release of the Dieckmann
CC       product intermediate (PubMed:29972614). The Diels-Alderase phm7 then
CC       uses the Dieckmann product of phm1 as substrate and catalyzes the
CC       Diels-Alder cycloaddition to form the decalin ring of N-
CC       desmethylphomasetin (PubMed:29972614, PubMed:34121297). N-
CC       desmethylphomasetin is further methylated to phomasetin by the
CC       methyltransferase phm5 (PubMed:29972614). {ECO:0000269|PubMed:29972614,
CC       ECO:0000269|PubMed:34121297}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:29972614}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of phomasetin.
CC       {ECO:0000269|PubMed:29972614}.
CC   -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC       family. {ECO:0000305}.
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DR   EMBL; LC361337; BBC43187.1; -; Genomic_DNA.
DR   SMR; A0A2Z5XAK4; -.
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; IPR013154; ADH_N.
DR   InterPro; IPR011032; GroES-like_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020843; PKS_ER.
DR   Pfam; PF08240; ADH_N; 1.
DR   Pfam; PF00107; ADH_zinc_N; 1.
DR   SMART; SM00829; PKS_ER; 1.
DR   SUPFAM; SSF50129; SSF50129; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   1: Evidence at protein level;
KW   NADP; Nucleotide-binding; Oxidoreductase.
FT   CHAIN           1..362
FT                   /note="Trans-enoyl reductase phm4"
FT                   /id="PRO_0000453338"
FT   BINDING         50..53
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         171..174
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         194..197
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         212
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         259..260
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT   BINDING         280..284
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255"
FT   BINDING         349..350
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ   SEQUENCE   362 AA;  38483 MW;  807AD213F2BEA243 CRC64;
     MPGIIDSSSK QSAIVGNSYG STELSHNVPI PHAEGDNVVV RTRAVSVNPV DAKMMGPYVT
     AGAIAGCDFA GEIEAIGPEA LSWGFKIGDR VCASIMGMNP LEPDHGAFAQ HVATHANALV
     RIPETMSFEE AAALCTCFMT CGLALFQSLG LPGSPVKPSA SATQVLVYGG ATATGTAAIQ
     LLRLAGFTPI ATCSPHSNEL VKTFGAEATF DYNDPECAAK IRAFTKNGLR YALDCITNRS
     SMQICYGSLG RVGGRYTALD PYPEDIAATR KIVKAAWVVG PIMLGHDIGW PAPHGRKADP
     DLFKFGMEWK KLVEGLMAKG VIKPHPLDVR KGGMERVIEC MEAIRAKEVN GKKLVVSLRE
     NH