PLE1_RHOPP
ID PLE1_RHOPP Reviewed; 523 AA.
AC A0A6S6QI82;
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 ple1 {ECO:0000303|PubMed:28924980};
DE EC=1.-.-.- {ECO:0000269|PubMed:28924980};
DE AltName: Full=Pleuromutilin biosynthesis cluster protein 1 {ECO:0000303|PubMed:28924980};
GN Name=ple1 {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; BCI98769.1; -; Genomic_DNA.
DR SMR; A0A6S6QI82; -.
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 ple1"
FT /id="PRO_0000453725"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 444
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 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 523 AA; 59035 MW; 4E8DB505998480B8 CRC64;
MAPSNTERAL PVLAIWAAIG LAYWIDSQKK KKHHLPPGPK KLPIIGNVMD LPAKIEWETY
ARWGKEYNSD IIQVSAVGTS IVILNSANAA NDLLLKRSAI YSSRPHSTMH HELSGWGFTW
ALMPYGESWR AGRRSFTKHF NSSNPGINQP RELRYVKRFL KQLYEKPNDV LDHVRNLVGS
TTLSMTYGLE TEPYNDPYVE LVEKAVLAAS EIMTSGAFLV DIIPAMKHIP PWVPGTIFHQ
KAALMRGHAY YVREQPFKVA QEMIKTGDYE PSFVSDALRD LENSETPEED LEHLKDVAGQ
VYIAGADTTA SALGTFFLAM VCFPEVQKKA QQELDSVLNG RLPEHADFPS FPYLNAVIKE
VYRWRPVTPM GVPHQTIADD VYRDYHIPKG SIVFANQWAM SNDENDYPQP GEFRPERYLT
EDGKPNKAVR DPFDIAFGFG RRICAGRYLA HSTITLAAAS VLSLFDLLKA VDENGKEIEP
TREYHQAMIS RPLEFPCRIK PRNKEAEEVI RACPLTFTKP TSA
