ID   PC15_PENCR              Reviewed;         271 AA.
AC   A0A0E3D8L9;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   24-JUN-2015, sequence version 1.
DT   03-AUG-2022, entry version 16.
DE   RecName: Full=Short-chain dehydrogenase PC-15 {ECO:0000303|PubMed:26213965};
DE            EC=1.1.1.- {ECO:0000305|PubMed:26213965};
DE   AltName: Full=Penitrem biosynthesis cluster protein PC-15 {ECO:0000303|PubMed:26213965};
GN   Name=PC-15 {ECO:0000303|PubMed:26213965};
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], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC   STRAIN=PN2402;
RX   PubMed=26213965; DOI=10.3390/toxins7082701;
RA   Nicholson M.J., Eaton C.J., Starkel C., Tapper B.A., Cox M.P., Scott B.;
RT   "Molecular cloning and functional analysis of gene clusters for the
RT   biosynthesis of indole-diterpenes in Penicillium crustosum and P.
RT   janthinellum.";
RL   Toxins 7:2701-2722(2015).
CC   -!- FUNCTION: Short-chain dehydrogenase; part of the gene cluster that
CC       mediates the biosynthesis of the indole diterpenes penitrems
CC       (PubMed:26213965). The geranylgeranyl diphosphate (GGPP) synthase penG
CC       catalyzes the first step in penitrem biosynthesis via conversion of
CC       farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl
CC       pyrophosphate (GGPP) (Probable). Condensation of indole-3-glycerol
CC       phosphate with GGPP by the prenyl transferase penC then forms 3-
CC       geranylgeranylindole (3-GGI) (Probable). Epoxidation by the FAD-
CC       dependent monooxygenase penM leads to a epoxidized-GGI that is
CC       substrate of the terpene cyclase penB for cyclization to yield
CC       paspaline (Probable). Paspaline is subsequently converted to 13-
CC       desoxypaxilline by the cytochrome P450 monooxygenase penP, the latter
CC       being then converted to paxilline by the cytochrome P450 monooxygenase
CC       penQ (PubMed:26213965). Paxilline is converted to beta-paxitriol via C-
CC       10 ketoreduction by the short-chain dehydrogenase PC-15 which can be
CC       monoprenylated at the C-20 by the indole diterpene prenyltransferase
CC       penD (Probable). A two-step elimination (acetylation and elimination)
CC       process performed by the O-acetyltransferase PC-16 and the
CC       P.simplicissimum ptmI-ortholog not yet identified in P.crustosum, leads
CC       to the production of the prenylated form of penijanthine (Probable).
CC       The FAD-linked oxidoreductase ptmO then converts the prenylated form of
CC       penijanthine into PC-M5 which is in turn transformed into PC-M4 by the
CC       aromatic dimethylallyltransferase PC-22 (Probable). A series of
CC       oxidation steps involving 4 cytochrome P450 monooxygenases (PC-21, PC-
CC       05, PC-23, PC-20) and a FAD-dependent monooxygenase (PC-14) are
CC       required for the transformation of PC-M4 to penitrems A and E.
CC       Synthesis of these final products is proposed to proceed via penitrems
CC       D and C (PC-21, PC-05, PC-14) and penitrems B and F (PC-21, PC-05, PC-
CC       14, PC-23) (Probable). {ECO:0000269|PubMed:26213965,
CC       ECO:0000305|PubMed:26213965}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:26213965}.
CC   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; KC963408; AGZ20196.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A0E3D8L9; -.
DR   SMR; A0A0E3D8L9; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
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   3: Inferred from homology;
KW   NAD; NADP; Oxidoreductase.
FT   CHAIN           1..271
FT                   /note="Short-chain dehydrogenase PC-15"
FT                   /id="PRO_0000446594"
FT   ACT_SITE        148
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT   BINDING         8..16
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         35..36
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         55..57
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   BINDING         181..183
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
SQ   SEQUENCE   271 AA;  29951 MW;  3E84ADD48DA8D8CF CRC64;
     MERRTVLITG CSQGGIGSAL AEVFHQRGFH VFATARKTEK MKHLRDLDRM TLIPLDVTQE
     SQISAAVELI QKHTGGTLDY LVNNAGDGYI IPVLDCDQLH GRQIFEVNFW GPLRMIQEFS
     PLLIAARGTI VNINSVASET LPLWLGIYSS SKAALLALSE TLRLELKPFG VQVLSVMTGA
     VQTMIFQTNY RLPPDSAYMT WEKQIAAQAE GSEKASRMSA TVYAERVVGD ILNRQGGITY
     RGQMASFAYW VVALMPRFLR ATPLLAQVGS Q