PRHH_PENBI
ID PRHH_PENBI Reviewed; 245 AA.
AC A0A1E1FFM9;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 25-MAY-2022, entry version 10.
DE RecName: Full=Terpene cyclase prhH {ECO:0000303|PubMed:27602587};
DE EC=4.2.3.- {ECO:0000305|PubMed:27602587};
DE AltName: Full=Paraherquonin biosynthesis cluster protein H {ECO:0000303|PubMed:27602587};
GN Name=prhH {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: Terpene cyclase; part of the gene cluster that mediates the
CC biosynthesis of paraherquonin, a meroterpenoid with a unique, highly
CC congested hexacyclic molecular architecture (PubMed:27602587). The
CC first step of the pathway is the synthesis of 3,5-dimethylorsellinic
CC acid (DMOA) by the polyketide synthase prhL (By similarity). Synthesis
CC of DMOA is followed by farnesylation by the prenyltransferase prhE,
CC methylesterification by the methyl-transferase prhM, epoxidation of the
CC prenyl chain by the flavin-dependent monooxygenase prhF, and
CC cyclization of the farnesyl moiety by the terpene cyclase prhH, to
CC yield the tetracyclic intermediate, protoaustinoid A (By similarity).
CC The short chain dehydrogenase prhI then oxidizes the C-3 alcohol group
CC of the terpene cyclase product to transform protoaustinoid A into
CC protoaustinoid B (PubMed:27602587). The FAD-binding monooxygenase prhJ
CC catalyzes the oxidation of protoaustinoid B into preaustinoid A which
CC is further oxidized into preaustinoid A1 by FAD-binding monooxygenase
CC phrK (PubMed:27602587). Finally, prhA leads to berkeleydione via the
CC berkeleyone B intermediate (PubMed:27602587, PubMed:29317628). PrhA is
CC a multifunctional dioxygenase that first desaturates at C5-C6 to form
CC berkeleyone B, followed by rearrangement of the A/B-ring to form the
CC cycloheptadiene moiety in berkeleydione (PubMed:27602587,
CC PubMed:29317628). Berkeleydione serves as the key intermediate for the
CC biosynthesis of paraherquonin as well as many other meroterpenoids
CC (Probable). The cytochrome P450 monooxygenases prhB, prhD, and prhN, as
CC well as the 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 -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:27602587}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the paxB family. {ECO:0000305}.
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DR EMBL; LC127182; BAV69309.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1E1FFM9; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR039020; PaxB-like.
DR PANTHER; PTHR42038; PTHR42038; 1.
PE 3: Inferred from homology;
KW Lyase; Membrane; Transmembrane; Transmembrane helix.
FT CHAIN 1..245
FT /note="Terpene cyclase prhH"
FT /id="PRO_0000449173"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 51..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 76..96
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 113..133
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 205..225
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 245 AA; 27678 MW; F682E48689405B63 CRC64;
MEEPLTVAAI FRDPFNILAI SEVLKVVAAV GWSVNYIGMV HRAWKDQIPS IGILPLCCDI
GWEFVYAWMF PDFSSHWQGV VRVWFFLHSA VLLVTLKVSP NDWVHTPLGH RHIVFIYIFV
TLVFGAGQYA LAAEIGPALG FHWGGALCQF LSSSCGIAQL LSRGHTRGAS YLIWFARAIS
TFAGFIKLCI RFQHNVDGAP WLDSPMCWFY IVTVLSFDAA YPFLYSSMRK LETPALRKES
RIKNQ
