PENB_PENTH
ID PENB_PENTH Reviewed; 445 AA.
AC A0A1B2CTB6;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Cytochrome P450 monooxygenase penB {ECO:0000303|PubMed:25859931};
DE EC=1.-.-.- {ECO:0000269|PubMed:25859931};
DE AltName: Full=Penigequinolones biosynthesis cluster protein B {ECO:0000303|PubMed:25859931};
GN Name=penB {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: Cytochrome P450 monooxygenase; 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). The first stage is catalyzed by the nonribosomal
CC pepdide synthetase penN that condenses anthranilic acid and O-methyl-L-
CC tyrosine to produce 4'-methoxycyclopeptin (By similarity). 4'-
CC methoxycyclopeptin is then converted to 4'-methoxydehydrocyclopeptin by
CC the ketoglutarate-dependent dioxygenase penM through dehydrogenation to
CC form a double bond between C-alpha and C-beta of the O-methyltyrosine
CC side chain (By similarity). PenM also converts its first product
CC methoxydehydrocyclopeptin to 4'-methoxycyclopenin (By similarity). The
CC following conversion of 4'methoxycyclopenin into 4'-methoxyviridicatin
CC is catalyzed by the cyclopenase penL (By similarity). 4'-
CC methoxyviridicatin is the precursor of quinolone natural products, and
CC is further converted to quinolinone B (Probable). The prenyltransferase
CC penI then catalyzes the canonical Friedel-Crafts alkylation of
CC quinolinone B with dimethylallyl cation to yield dimethylallyl
CC quinolone, which is subjected to FAD-dependent dehydrogenation by the
CC FAD-linked oxidoreductase penH to yield conjugated aryl diene
CC (PubMed:25859931). The delta(3') double bond then serves as the site of
CC the second alkylation with DMAPP catalyzed by the prenyltransferase
CC penG to yield a carbenium ion intermediate, which can be attacked by
CC H(2)O to yield a styrenyl quinolone containing a C3'-hydroxyprenyl
CC chain, or undergo cyclization to yield yaequinolones J1 and J2
CC (PubMed:25859931). The conversion of the styrenyl quinolone into the
CC tetrahydrofuran-containing yaequinolone C is performed by the FAD-
CC dependent monooxygenase penE and involves epoxidation of the terminal
CC C7'-C8' olefin, followed by epoxide ring opening initiated by the C3'
CC hydroxyl group (PubMed:25859931). The predicted cysteine hydrolase penJ
CC acts as an epoxide hydrolase that enhances the rate of the 5-exo-tet
CC cyclization step, increasing the yield of yaequinolone C
CC (PubMed:25859931, PubMed:28114276). PenF catalyzes the cationic
CC rearrangement of the epoxide formed by penE (before ring opening to
CC produce yaequinolone C) into yaequinolone D (PubMed:28114276). Finally,
CC the short-chain dehydrogenase/reductase (SDR)-like reductase penD,
CC catalyzes both the dehydration of yaequinolone D and the reduction of
CC the resulting oxonium to yield penigequinolone (PubMed:28114276).
CC {ECO:0000250|UniProtKB:C8VJQ3, ECO:0000250|UniProtKB:Q5AR53,
CC ECO:0000250|UniProtKB:Q5AR54, ECO:0000269|PubMed:25859931,
CC ECO:0000269|PubMed:28114276, ECO:0000305|PubMed:25859931}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
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 -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; KX528209; ANY57880.1; -; Genomic_DNA.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase.
FT CHAIN 1..445
FT /note="Cytochrome P450 monooxygenase penB"
FT /id="PRO_0000455354"
FT BINDING 381
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 445 AA; 50523 MW; 0A7C58EC6AE26A8B CRC64;
MHATYKSAIV RTGPNQVHVN DPEVYKNTFA SASPFDKSRF FYSSVGVGDA IGAIMDRKQH
HIRRTLLSPG LRANVILSYS PNLHKLVMNC ADVMSGQARQ AKSINLLRYT RSLTVDVIGD
FTFGRPMGLV NEEDEMPELI RDLQDFSSQF HLWKHFPLLR KLVTAIPKSI SRKWMPGFVQ
LREKSTAAVN EYLAGKQAGK PVSNTLKEGT FLDLLLNPPE KITSEAPKPS VLIDEGCAFI
TGGSDTTGFT MENATYLVLR HPSCLQKLRQ ELDEASRHIK DVFSPQHLLQ LPFLSAVVKE
TLRLYTPAAS PLPRTVPDDG VMIHGHFLPD GTILTHSLYL IHHNPNFFTN PKSFQPERWL
GSSAKDLEQY YVPFSKGSRS CIGMTLAYHE IYTYLAIVFS RFDMELFNTT DRDMEWRDHF
FVKRKGVLKV RIVRDRWSGE EFTSP
