PENM_PENTH
ID PENM_PENTH Reviewed; 312 AA.
AC A0A1B2CTC6;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Iron/alpha-ketoglutarate-dependent dioxygenase penM {ECO:0000303|PubMed:25859931};
DE EC=1.14.-.- {ECO:0000250|UniProtKB:Q5AR53};
DE AltName: Full=Penigequinolones biosynthesis cluster protein M {ECO:0000303|PubMed:25859931};
GN Name=penM {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.
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: Iron/alpha-ketoglutarate-dependent dioxygenase; part of the
CC gene cluster that mediates the biosynthesis of penigequinolones, potent
CC insecticidal alkaloids that contain a highly modified 10-carbon prenyl
CC group (PubMed:25859931). 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 -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q5AR53};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:25859931}.
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000305|PubMed:25859931}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:25859931}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q4WAW9}.
CC -!- SIMILARITY: Belongs to the PhyH family. {ECO:0000305}.
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DR EMBL; KX528209; ANY57891.1; -; Genomic_DNA.
DR GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR InterPro; IPR008775; Phytyl_CoA_dOase.
DR Pfam; PF05721; PhyH; 1.
PE 3: Inferred from homology;
KW Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT CHAIN 1..312
FT /note="Iron/alpha-ketoglutarate-dependent dioxygenase penM"
FT /id="PRO_0000455369"
FT REGION 287..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 134
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q5AR53"
FT BINDING 136
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q5AR53"
FT BINDING 211
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250|UniProtKB:Q5AR53"
SQ SEQUENCE 312 AA; 34607 MW; E3994BF2DFB294AF CRC64;
MTIQDHTKRK IPRLSATRDC HEIWPTVQEH GAVIIKNLLP LEVVQRLNRE VDPYVKIEPI
PAAETKDHPN RVLSTTTRMI NVLADFSKAY REDVLNNETL NKVSTDAFSV YGDYWVLMGA
VMELAPTNPA QPLHRDMRFS HPLVDYLKHD APPTSINLLI ALTPFTVENG ATHVILGSHK
WPDLSGATME QTVRAVMEPG DAVLITDNTV HCGGADMTGT ETRRLLSLTM GISQITPLES
NFTVPRPIIE SLTPLAQRLV GWRSQRSSVP RDIGLLTIRG KSIENTLGLK SEQPLPDGME
KGSMQETDIG GQ
