ID   PLE7_RHOPP              Reviewed;         253 AA.
AC   A0A6S6QNE4;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   02-DEC-2020, sequence version 1.
DT   03-AUG-2022, entry version 6.
DE   RecName: Full=Short chain dehydrogenase ple7 {ECO:0000303|Ref.1};
DE            EC=1.1.1.- {ECO:0000269|Ref.1};
DE   AltName: Full=Pleuromutilin biosynthesis cluster protein 7 {ECO:0000303|Ref.1};
GN   Name=ple7 {ECO:0000303|Ref.1};
OS   Rhodocybe pseudopiperita (Clitopilus pseudopiperitus).
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC   Agaricomycetidae; Agaricales; Entolomataceae; Rhodocybe.
OX   NCBI_TaxID=693819;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP   PATHWAY.
RC   STRAIN=ATCC 20527;
RA   Yamane M., Minami A., Liu C., Ozaki T., Takeuchi I., Tsukagoshi T.,
RA   Tokiwano T., Gomi K., Oikawa H.;
RT   "Biosynthetic machinery of diterpene pleuromutilin isolated from
RT   basidiomycete fungi.";
RL   ChemBioChem 18:2317-2322(2017).
CC   -!- FUNCTION: Short chain dehydrogenase; part of the gene cluster that
CC       mediates the biosynthesis of pleuromutilin, a tricyclic diterpene
CC       showing antibacterial properties (Ref.1). The geranylgeranyl
CC       diphosphate (GGPP) synthase ple4 catalyzes the first step in
CC       pleuromutilin biosynthesis (Ref.1). GGPP is then substrate of the
CC       premutilin synthase (PS) ple3 to yield premutilin (Ref.1). Premutilin
CC       synthase is a bifunctional enzyme composed of the fusion of a class II
CC       diterpene cyclase (DTC) and a class I diterpene synthase (DTS), with
CC       the corresponding domains and active sites containing characteristic
CC       aspartate-rich motifs (By similarity). GGPP is first converted to
CC       mutildienyl-diphosphate (MPP) at the class II DTC site (By similarity).
CC       MPP is subsequently further cyclized at the class I DTS site, followed
CC       by a 1,5-hydride shift and addition of water prior to terminating
CC       deprotonation, to yield premutilin (By similarity). The cytochrome P450
CC       monooxygenases ple5 and ple6 hydroxylate premutilin at C-11 and C-3,
CC       respectively, producing 11-hydroxypremutilin and 3-hydroxypremutilin
CC       (Ref.1). The combination of the actions of both ple5 and ple6 leads to
CC       the production of 3,11-dihydroxypremutilin (Ref.1). The short chain
CC       dehydrogenase ple7 further converts 3,11-dihydroxypremutilin into
CC       mutilin (Ref.1). The acetyltransferase ple2 then acetylates mutilin to
CC       produce 14-O-acetylmutilin (Ref.1). Finally, the cytochrome P450
CC       monooxygenase ple1 catalyzes hydroxylation on the alpha position of the
CC       acetyl side chain of 14-O-acetylmutilin to yield pleuromutilin (Ref.1).
CC       {ECO:0000250|UniProtKB:A0A2L0VXR0, ECO:0000269|Ref.1}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|Ref.1}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC       protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; LC314149; BCI98775.1; -; Genomic_DNA.
DR   SMR; A0A6S6QNE4; -.
DR   UniPathway; UPA00213; -.
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; IPR020904; Sc_DH/Rdtase_CS.
DR   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   PRINTS; PR00080; SDRFAMILY.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   PROSITE; PS00061; ADH_SHORT; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Membrane; NAD; Oxidoreductase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..253
FT                   /note="Short chain dehydrogenase ple7"
FT                   /id="PRO_0000453728"
FT   TRANSMEM        5..25
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        148
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT   BINDING         7..15
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         34..35
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         52..54
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         135
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         148..152
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   CARBOHYD        187
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   253 AA;  26622 MW;  9CED6C64A49ECA33 CRC64;
     MEGKIVIVTG ASHGIGLATV NLLLAAGASV FGVDLAPTPP SVTSEKFKFL QLNICDKDAP
     AKIVLGSKDA FGSDRIDALL NVAGISDYFQ TALTFEDDVW DSVIDVNLAA QVRLMREVLK
     VMKVQKSGSI VNVVSKLALS GACGGVAYVA SKHALLGVTK NTAWMFKDDG IRCNAVAPGS
     TDTNIRNTTD ATKIDYDAFT RAMPVIGVHC NLQTGEGMMS PEPAAQAIFF LASDLSKGMN
     GVVIPVDNAW SVI