PRHC_PENBI
ID PRHC_PENBI Reviewed; 174 AA.
AC A0A1E1FFL1;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 18-JAN-2017, sequence version 1.
DT 25-MAY-2022, entry version 17.
DE RecName: Full=Isomerase prhC {ECO:0000303|PubMed:27602587};
DE EC=5.-.-.- {ECO:0000305|PubMed:28759016};
DE AltName: Full=Paraherquonin biosynthesis cluster protein C {ECO:0000303|PubMed:27602587};
GN Name=prhC {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=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).
RN [3] {ECO:0007744|PDB:5X9J}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS), SUBUNIT, FUNCTION, CATALYTIC
RP ACTIVITY, AND PATHWAY.
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).
CC -!- FUNCTION: Isomerase; 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 -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:28759016}.
CC -!- SIMILARITY: Belongs to the trt14 isomerase family. {ECO:0000305}.
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DR EMBL; LC127182; BAV69304.1; -; Genomic_DNA.
DR PDB; 5X9J; X-ray; 2.10 A; A/B=1-174.
DR PDBsum; 5X9J; -.
DR AlphaFoldDB; A0A1E1FFL1; -.
DR SMR; A0A1E1FFL1; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
PE 1: Evidence at protein level;
KW 3D-structure; Isomerase.
FT CHAIN 1..174
FT /note="Isomerase prhC"
FT /id="PRO_0000449169"
FT HELIX 6..23
FT /evidence="ECO:0007829|PDB:5X9J"
FT HELIX 26..31
FT /evidence="ECO:0007829|PDB:5X9J"
FT STRAND 33..41
FT /evidence="ECO:0007829|PDB:5X9J"
FT HELIX 53..66
FT /evidence="ECO:0007829|PDB:5X9J"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:5X9J"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:5X9J"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:5X9J"
FT TURN 84..87
FT /evidence="ECO:0007829|PDB:5X9J"
FT STRAND 88..99
FT /evidence="ECO:0007829|PDB:5X9J"
FT STRAND 104..114
FT /evidence="ECO:0007829|PDB:5X9J"
FT STRAND 120..128
FT /evidence="ECO:0007829|PDB:5X9J"
FT HELIX 130..141
FT /evidence="ECO:0007829|PDB:5X9J"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:5X9J"
FT HELIX 147..153
FT /evidence="ECO:0007829|PDB:5X9J"
SQ SEQUENCE 174 AA; 19262 MW; D93C6FEE29CBCA63 CRC64;
MASNSTREKL IALAHKFCSI ISSGDMEAVL ALRTESCLTY QCCPSFSTRP LNNQETREYF
EEWKHIGWNS KFWIIDEGTM VVDEAAKKIA FRAACSADTI GGPYENENLV ILQATDDCAL
VDGIWEFFDA VRKQDLMNRL AAKQAAKGLD SWCANTHSGD DKGVPANNES KVAA
