PTMH_PENSI
ID PTMH_PENSI Reviewed; 271 AA.
AC A0A140JWS5;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Short-chain dehydrogenase ptmH {ECO:0000303|PubMed:25831977};
DE EC=1.1.1.- {ECO:0000269|PubMed:25831977};
DE AltName: Full=Penitrem biosynthesis cluster 1 protein H {ECO:0000303|PubMed:25831977};
GN Name=ptmH {ECO:0000303|PubMed:25831977};
OS Penicillium simplicissimum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=69488;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, FUNCTION, AND PATHWAY.
RC STRAIN=AK-40;
RX PubMed=25831977; DOI=10.1002/anie.201501072;
RA Liu C., Tagami K., Minami A., Matsumoto T., Frisvad J.C., Suzuki H.,
RA Ishikawa J., Gomi K., Oikawa H.;
RT "Reconstitution of biosynthetic machinery for the synthesis of the highly
RT elaborated indole diterpene penitrem.";
RL Angew. Chem. Int. Ed. 54:5748-5752(2015).
CC -!- FUNCTION: Short-chain dehydrogenase; part of the gene cluster that
CC mediates the biosynthesis of the indole diterpenes penitrems
CC (PubMed:25831977). The geranylgeranyl diphosphate (GGPP) synthase ptmG
CC catalyzes the first step in penitrem biosynthesis via conversion of
CC farnesyl pyrophosphate and isopentyl pyrophosphate into geranylgeranyl
CC pyrophosphate (GGPP) (PubMed:25831977). Condensation of indole-3-
CC glycerol phosphate with GGPP by the prenyl transferase ptmC then forms
CC 3-geranylgeranylindole (3-GGI) (PubMed:25831977). Epoxidation by the
CC FAD-dependent monooxygenase ptmM leads to a epoxidized-GGI that is
CC substrate of the terpene cyclase ptmB for cyclization to yield
CC paspaline (PubMed:25831977). Paspaline is subsequently converted to 13-
CC desoxypaxilline by the cytochrome P450 monooxygenase ptmP, the latter
CC being then converted to paxilline by the cytochrome P450 monooxygenase
CC ptmQ (PubMed:25831977). Paxilline is converted to beta-paxitriol via C-
CC 10 ketoreduction by the short-chain dehydrogenase ptmH which can be
CC monoprenylated at the C-20 by the indole diterpene prenyltransferase
CC ptmD (PubMed:25831977). A two-step elimination (acetylation and
CC elimination) process performed by the O-acetyltransferase ptmV and ptmI
CC leads to the production of the prenylated form of penijanthine
CC (PubMed:25831977). The FAD-linked oxidoreductase ptmO then converts the
CC prenylated form of penijanthine into PC-M5 which is in turn transformed
CC into PC-M4 by the aromatic dimethylallyltransferase ptmE
CC (PubMed:25831977). Five sequential oxidative transformations performed
CC by the cytochrome P450 monooxygenases ptmK, ptmU, ptmL, ptmN and ptmJ
CC yield the various penitrem compounds. PtmK, ptmU and ptmM are involved
CC in the formation of the key bicyclic ring of penitrem C via the
CC formation of the intermediates secopenitrem D and penitrem D. PtmL
CC catalyzes the epoxidation of penitrem D and C to yield penitrem B and
CC F, respectively. PtmJ catalyzes the last benzylic hydroxylation to
CC convert penitrem B to prenitrem E and penitrem F to penitrem A
CC (PubMed:25831977). {ECO:0000269|PubMed:25831977}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:25831977}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; LC027936; BAU61552.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A140JWS5; -.
DR SMR; A0A140JWS5; -.
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 ptmH"
FT /id="PRO_0000446593"
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; 29927 MW; 9AE8DEA2DF1703FD CRC64;
MERRTVLITG CSQGGIGSAL AEAFHQRGFH VFATARKTEK MTHLRDLDWM TLIPLDVTQE
SQISAAVELI QKHTGGTLDY LVNNAGDGYI IPVLDCDQVH GRQIFEVNFW GPLRMIQEFS
PLLIAARGTI VNINSVASET LPLWLGIYSS SKAALLALSE TLRLELKPFG VQVLSVMTGA
VQTMIFQTNY RLPPDSAYVA WEKQIAAQAE GSEQASRMSA TVYAERVVGD ILNRRGGITY
RGQMASFAYW VVALMPRFLR DLVTVKMAGI S
