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 27-MAR-2024, entry version 21.
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 GO; GO:0044249; P:cellular biosynthetic process; IEA:UniProt.
DR GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR CDD; cd05374; 17beta-HSD-like_SDR_c; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR PANTHER; PTHR44169; NADPH-DEPENDENT 1-ACYLDIHYDROXYACETONE PHOSPHATE REDUCTASE; 1.
DR PANTHER; PTHR44169:SF16; OXIDOREDUCTASE, SHORT-CHAIN DEHYDROGENASE_REDUCTASE FAMILY (AFU_ORTHOLOGUE AFUA_2G14460); 1.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 3: Inferred from homology;
KW 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 ACT_SITE 152
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 8
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:L0E2Z4"
FT BINDING 34
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:L0E2Z4"
FT BINDING 40
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:L0E2Z4"
FT BINDING 56
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:L0E2Z4"
FT BINDING 84
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 148
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 152
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 181
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O93868"
FT BINDING 183
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:L0E2Z4"
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
//
