PRHD_PENBI
ID PRHD_PENBI Reviewed; 511 AA.
AC A0A1E1FFL4;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Cytochrome P450 monooxygenase prhD {ECO:0000303|PubMed:27602587};
DE EC=1.-.-.- {ECO:0000305|PubMed:27602587};
DE AltName: Full=Paraherquonin biosynthesis cluster protein D {ECO:0000303|PubMed:27602587};
GN Name=prhD {ECO:0000303|PubMed:27602587};
OS Penicillium brasilianum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=104259;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=ATCC 22354 / NBRC 6234 / CBS 338.59 / FRR 3454 / IMI 68220;
RX PubMed=27602587; DOI=10.1021/jacs.6b08424;
RA Matsuda Y., Iwabuchi T., Fujimoto T., Awakawa T., Nakashima Y., Mori T.,
RA Zhang H., Hayashi F., Abe I.;
RT "Discovery of key dioxygenases that diverged the paraherquonin and
RT acetoxydehydroaustin pathways in Penicillium brasilianum.";
RL J. Am. Chem. Soc. 138:12671-12677(2016).
RN [2]
RP FUNCTION.
RX PubMed=28759016; DOI=10.1038/nchembio.2443;
RA Mori T., Iwabuchi T., Hoshino S., Wang H., Matsuda Y., Abe I.;
RT "Molecular basis for the unusual ring reconstruction in fungal
RT meroterpenoid biogenesis.";
RL Nat. Chem. Biol. 13:1066-1073(2017).
RN [3]
RP FUNCTION.
RX PubMed=29317628; DOI=10.1038/s41467-017-02371-w;
RA Nakashima Y., Mori T., Nakamura H., Awakawa T., Hoshino S., Senda M.,
RA Senda T., Abe I.;
RT "Structure function and engineering of multifunctional non-heme iron
RT dependent oxygenases in fungal meroterpenoid biosynthesis.";
RL Nat. Commun. 9:104-104(2018).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of paraherquonin, a meroterpenoid with a
CC unique, highly congested hexacyclic molecular architecture
CC (PubMed:27602587). The first step of the pathway is the synthesis of
CC 3,5-dimethylorsellinic acid (DMOA) by the polyketide synthase prhL (By
CC similarity). Synthesis of DMOA is followed by farnesylation by the
CC prenyltransferase prhE, methylesterification by the methyl-transferase
CC prhM, epoxidation of the prenyl chain by the flavin-dependent
CC monooxygenase prhF, and cyclization of the farnesyl moiety by the
CC terpene cyclase prhH, to yield the tetracyclic intermediate,
CC protoaustinoid A (By similarity). The short chain dehydrogenase prhI
CC then oxidizes the C-3 alcohol group of the terpene cyclase product to
CC transform protoaustinoid A into protoaustinoid B (PubMed:27602587). The
CC FAD-binding monooxygenase prhJ catalyzes the oxidation of
CC protoaustinoid B into preaustinoid A which is further oxidized into
CC preaustinoid A1 by FAD-binding monooxygenase phrK (PubMed:27602587).
CC Finally, prhA leads to berkeleydione via the berkeleyone B intermediate
CC (PubMed:27602587, PubMed:29317628). PrhA is a multifunctional
CC dioxygenase that first desaturates at C5-C6 to form berkeleyone B,
CC followed by rearrangement of the A/B-ring to form the cycloheptadiene
CC moiety in berkeleydione (PubMed:27602587, PubMed:29317628).
CC Berkeleydione serves as the key intermediate for the biosynthesis of
CC paraherquonin as well as many other meroterpenoids (Probable). The
CC cytochrome P450 monooxygenases prhB, prhD, and prhN, as well as the
CC isomerase prhC, are probably involved in the late stage of
CC paraherquonin biosynthesis, after the production of berkeleydione
CC (Probable). Especially prhC might be a multifunctional enzyme that
CC catalyzes the D-ring expansion via intramolecular methoxy
CC rearrangement, as well as the hydrolysis of the expanded D-ring
CC (Probable). {ECO:0000250|UniProtKB:Q5ATJ7, ECO:0000269|PubMed:27602587,
CC ECO:0000269|PubMed:29317628, ECO:0000305|PubMed:27602587,
CC ECO:0000305|PubMed:28759016, ECO:0000305|PubMed:29317628}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:27602587}.
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; LC127182; BAV69305.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1E1FFL4; -.
DR SMR; A0A1E1FFL4; -.
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; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..511
FT /note="Cytochrome P450 monooxygenase prhD"
FT /id="PRO_0000449164"
FT TRANSMEM 10..30
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 7
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 502
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 511 AA; 58897 MW; F4E736088C1C7516 CRC64;
MHQLLENLSG NGMGLLIPLG LSWLIWTILL PKQQYRGKLF NDRARFEWFY TKARRRFLEN
GGVILNNAFK KSENSFYVMT SREVEIVLNP KYMNEVRNDD RFAVTERVDQ LLHGDVPGFG
IIKHSAQTHK IFSNTFQSRV VREIGTFLVP IFEEIDHFLE TQWTDNEEWH AFSLHPSMVQ
LVSQESTRLF LGPEMCRDAH WLQASVKYIQ SFFMGIDLLD SWRPIFRPLV SKFSKTGKQI
RSDLAEARQI LSPFIADRQA RKAKGEKFND LLQWFDDAAR GAEYDAPLLI LRSSMAAVHS
TSDLLTKAIF EICTQPGLID DIREEAIRVF KEHGLRQTAI QELRLTDSVL KETQRLKPLQ
TTAFIRLTKE DVVLSDGLEI PKGTPIRISN HHMWDPEVSE YPNADQFDGY RFYKLRQVPG
QEQTAQLATV SPSHTGFGLG KHACPGRFFA ATATKVILCK ILLDYDLKLL DGQRPKTMWR
GDAQVPDPMC QIVVRRRKEE FNLSSLLHDV K
