PEND_PENTH
ID PEND_PENTH Reviewed; 277 AA.
AC A0A1B2CTA9;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 1.
DT 03-AUG-2022, entry version 11.
DE RecName: Full=Short chain dehydrogenase penD {ECO:0000303|PubMed:25859931};
DE EC=1.1.1.- {ECO:0000269|PubMed:28114276};
DE AltName: Full=Penigequinolones biosynthesis cluster protein D {ECO:0000303|PubMed:25859931};
GN Name=penD {ECO:0000303|PubMed:25859931};
OS Penicillium thymicola.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=293382;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=IBT 5891 / CBS 111225;
RX PubMed=25859931; DOI=10.1021/jacs.5b03022;
RA Zou Y., Zhan Z., Li D., Tang M., Cacho R.A., Watanabe K., Tang Y.;
RT "Tandem prenyltransferases catalyze isoprenoid elongation and complexity
RT generation in biosynthesis of quinolone alkaloids.";
RL J. Am. Chem. Soc. 137:4980-4983(2015).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=28114276; DOI=10.1038/nchembio.2283;
RA Zou Y., Garcia-Borras M., Tang M.C., Hirayama Y., Li D.H., Li L.,
RA Watanabe K., Houk K.N., Tang Y.;
RT "Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid
RT biosynthesis.";
RL Nat. Chem. Biol. 13:325-332(2017).
CC -!- FUNCTION: Short chain dehydrogenase; part of the gene cluster that
CC mediates the biosynthesis of penigequinolones, potent insecticidal
CC alkaloids that contain a highly modified 10-carbon prenyl group
CC (PubMed:25859931, PubMed:28114276). The first stage is catalyzed by the
CC nonribosomal pepdide synthetase penN that condenses anthranilic acid
CC and O-methyl-L-tyrosine to produce 4'-methoxycyclopeptin (By
CC similarity). 4'-methoxycyclopeptin is then converted to 4'-
CC methoxydehydrocyclopeptin by the ketoglutarate-dependent dioxygenase
CC penM through dehydrogenation to form a double bond between C-alpha and
CC C-beta of the O-methyltyrosine side chain (By similarity). PenM also
CC converts its first product methoxydehydrocyclopeptin to 4'-
CC methoxycyclopenin (By similarity). The following conversion of
CC 4'methoxycyclopenin into 4'-methoxyviridicatin is catalyzed by the
CC cyclopenase penL (By similarity). 4'-methoxyviridicatin is the
CC precursor of quinolone natural products, and is further converted to
CC quinolinone B (Probable). The prenyltransferase penI then catalyzes the
CC canonical Friedel-Crafts alkylation of quinolinone B with dimethylallyl
CC cation to yield dimethylallyl quinolone, which is subjected to FAD-
CC dependent dehydrogenation by the FAD-linked oxidoreductase penH to
CC yield conjugated aryl diene (PubMed:25859931). The delta(3') double
CC bond then serves as the site of the second alkylation with DMAPP
CC catalyzed by the prenyltransferase penG to yield a carbenium ion
CC intermediate, which can be attacked by H(2)O to yield a styrenyl
CC quinolone containing a C3'-hydroxyprenyl chain, or undergo cyclization
CC to yield yaequinolones J1 and J2 (PubMed:25859931). The conversion of
CC the styrenyl quinolone into the tetrahydrofuran-containing yaequinolone
CC C is performed by the FAD-dependent monooxygenase penE and involves
CC epoxidation of the terminal C7'-C8' olefin, followed by epoxide ring
CC opening initiated by the C3' hydroxyl group (PubMed:25859931). The
CC predicted cysteine hydrolase penJ acts as an epoxide hydrolase that
CC enhances the rate of the 5-exo-tet cyclization step, increasing the
CC yield of yaequinolone C (PubMed:25859931, PubMed:28114276). PenF
CC catalyzes the cationic rearrangement of the epoxide formed by penE
CC (before ring opening to produce yaequinolone C) into yaequinolone D
CC (PubMed:28114276). Finally, the short-chain dehydrogenase/reductase
CC (SDR)-like reductase penD, catalyzes both the dehydration of
CC yaequinolone D and the reduction of the resulting oxonium to yield
CC penigequinolone (PubMed:28114276). {ECO:0000250|UniProtKB:C8VJQ3,
CC ECO:0000250|UniProtKB:Q5AR53, ECO:0000250|UniProtKB:Q5AR54,
CC ECO:0000269|PubMed:25859931, ECO:0000269|PubMed:28114276,
CC ECO:0000305|PubMed:25859931}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:28114276}.
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:28114276}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:28114276}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; KX528209; ANY57882.1; -; Genomic_DNA.
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 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 NAD; Oxidoreductase.
FT CHAIN 1..277
FT /note="Short chain dehydrogenase penD"
FT /id="PRO_0000455357"
FT ACT_SITE 173
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 20..28
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 47..48
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 78..80
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 277 AA; 29008 MW; D6D2923D993E3F4B CRC64;
MPLSSKVSQA PWSLTGKTAV VTGGSRGIGR AIAIHLARKG VRKLAITYVR DLASAESALE
EIRKEGIETG IAIQADILNA SVGRDLIAQA LVGLETSTID ILVNNAALLD PINTPSVEDV
TLENFQELMQ ANCFAPVSII NACMPHLPPS GGRVINISSV ASKTPNPGTI VTYGASKAAL
DSYTRSMAGL FAKDKTATFN TVCVGPTVTD SFRAVSQLYP GEFIKEVAKS FTAADRVGVP
EDIAYIVGFL ASEEGRWMNG ACVSANGGLR EALPALS
