PLE6_RHOPP
ID PLE6_RHOPP Reviewed; 525 AA.
AC A0A6S6QP77;
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 ple6 {ECO:0000303|PubMed:28924980};
DE EC=1.-.-.- {ECO:0000269|PubMed:28924980};
DE AltName: Full=Pleuromutilin biosynthesis cluster protein 6 {ECO:0000303|PubMed:28924980};
GN Name=ple6 {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; BCI98774.1; -; Genomic_DNA.
DR SMR; A0A6S6QP77; -.
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 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..525
FT /note="Cytochrome P450 monooxygenase ple6"
FT /id="PRO_0000453727"
FT TRANSMEM 15..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 455
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 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 525 AA; 59955 MW; C1F2D3FF672D97C4 CRC64;
MNLSEIKAAL LERNMFAPVA IPVACYLVYK LLRMGSREKT LPPGPPTKPV LGNLHQMPAM
NDMHLQLSKW AQEYGGIYSL KIFFKNVVIL TDSASVTGIL DKLNAKTAER PTGFLPAPIK
DDRFLPIALY KSDEFRINHK AFKLLISNDS IDRYAENIET ETIVLMKELL AEPKEFFRHL
VRTSMSSIVA IAYGERILTS SDPFIPYHEE YLHDFENMMG LRGVHFTALI PWLAKWLPDS
LAGWRVMAQG IKDKQLGIFN DFLGRVEKRM EAGIFDGSHM QTILQKKEEL GFKDRDLIAY
HGGVMIDGGT DTLAMFTRVF VLMMTMHPEC QQKIRDELKE VMGDEYDSRL PTYEDALKMK
YFNCVIREVT RIWPPSPIVP PHYSTEDLEY DGYFIPKGTV IVMNLYGIQR DPKVFDAPDE
FRPERYMESE FGTKPGVDLT GYRHTFTFGA GRRICPGLKM AEIFKRTVSL NIIWGFDIKP
LPNSPKSMKD DVVVPGPVSM PKPFECEMVP RSQAVVQVIH EVADY
