PLE5_RHOPP
ID PLE5_RHOPP Reviewed; 523 AA.
AC A0A6S6QPY4;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-DEC-2020, sequence version 1.
DT 03-AUG-2022, entry version 6.
DE RecName: Full=Cytochrome P450 monooxygenase ple5B {ECO:0000303|PubMed:28924980};
DE EC=1.-.-.- {ECO:0000269|PubMed:28924980};
DE AltName: Full=Pleuromutilin biosynthesis cluster protein 5 {ECO:0000303|PubMed:28924980};
GN Name=ple5 {ECO:0000303|PubMed:28924980};
OS Rhodocybe pseudopiperita (Clitopilus pseudopiperitus).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Entolomataceae; Rhodocybe.
OX NCBI_TaxID=693819;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=ATCC 20527;
RX PubMed=28924980; DOI=10.1002/cbic.201700434;
RA Yamane M., Minami A., Liu C., Ozaki T., Takeuchi I., Tsukagoshi T.,
RA Tokiwano T., Gomi K., Oikawa H.;
RT "Biosynthetic machinery of diterpene pleuromutilin isolated from
RT basidiomycete fungi.";
RL ChemBioChem 18:2317-2322(2017).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of pleuromutilin, a tricyclic diterpene
CC showing antibacterial properties (PubMed:28924980). The geranylgeranyl
CC diphosphate (GGPP) synthase ple4 catalyzes the first step in
CC pleuromutilin biosynthesis (PubMed:28924980). GGPP is then substrate of
CC the premutilin synthase (PS) ple3 to yield premutilin
CC (PubMed:28924980). Premutilin synthase is a bifunctional enzyme
CC composed of the fusion of a class II diterpene cyclase (DTC) and a
CC class I diterpene synthase (DTS), with the corresponding domains and
CC active sites containing characteristic aspartate-rich motifs (By
CC similarity). GGPP is first converted to mutildienyl-diphosphate (MPP)
CC at the class II DTC site (By similarity). MPP is subsequently further
CC cyclized at the class I DTS site, followed by a 1,5-hydride shift and
CC addition of water prior to terminating deprotonation, to yield
CC premutilin (By similarity). The cytochrome P450 monooxygenases ple5 and
CC ple6 hydroxylate premutilin at C-11 and C-3, respectively, producing
CC 11-hydroxypremutilin and 3-hydroxypremutilin (PubMed:28924980). The
CC combination of the actions of both ple5 and ple6 leads to the
CC production of 3,11-dihydroxypremutilin (PubMed:28924980). The short
CC chain dehydrogenase ple7 further converts 3,11-dihydroxypremutilin into
CC mutilin (PubMed:28924980). The acetyltransferase ple2 then acetylates
CC mutilin to produce 14-O-acetylmutilin (PubMed:28924980). Finally, the
CC cytochrome P450 monooxygenase ple1 catalyzes hydroxylation on the alpha
CC position of the acetyl side chain of 14-O-acetylmutilin to yield
CC pleuromutilin (PubMed:28924980). {ECO:0000250|UniProtKB:A0A2L0VXR0,
CC ECO:0000269|PubMed:28924980}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:28924980}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; LC314149; BCI98773.1; -; Genomic_DNA.
DR SMR; A0A6S6QPY4; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..523
FT /note="Cytochrome P450 monooxygenase ple5B"
FT /id="PRO_0000453726"
FT TRANSMEM 16..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 446
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"
FT CARBOHYD 82
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 523 AA; 58303 MW; ADCB8732F6B8E975 CRC64;
MLSVDLPSVA NLDPRIAAAA AGSAVAVYKL LQLGSRESFL PPGPPTRPVL GNAHLMTKMW
LPMQLTEWAR EYGEVYSLKL MNRTVIVLNS PKAVRTILDK QGNITGDRPF SPMISRYTEG
LNLTVESMDT SVWKTGRKGI HNYLTPSALS GYVPRQEEES VNLMHDLLMD APNRPIHIRR
AMMSLLLHIV YGQPRCESYY GTVIENAYEA ATRIGQIAHN GAAVDAFPFL DYIPRGFPGA
GWKTIVDEFK DFRNSVYNSL LDGAKKAMDS GIRTGCFAES VIDHPDGRSW LELSNLSGGF
LDAGAKTTIS YIESCILALI AHPDCQRKIQ DELDHVLGTE TMPCFDDLER LPYLKAFLQE
VLRLRPVGPV ALPHVSRENL SYGGHVLPEG SMIFMNIWGM GHDPELFDEP EAFKPERYLL
TSNGTKPGLS EDVNPDFLFG AGRRVCPGDK LAKRSTGLFI MRLCWAFNFY PDSSNKDTVK
NMNMEDCYDK SVSLETLPLP FACKIEPRDK MKEDLIKEAF AAL
