PRHJ_PENBI
ID PRHJ_PENBI Reviewed; 641 AA.
AC A0A1E1FFN7;
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=FAD-binding monooxygenase prhJ {ECO:0000303|PubMed:27602587};
DE EC=1.14.13.- {ECO:0000269|PubMed:27602587};
DE AltName: Full=Paraherquonin biosynthesis cluster protein J {ECO:0000303|PubMed:27602587};
GN Name=prhJ {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, CATALYTIC ACTIVITY, AND
RP 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: FAD-binding 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 -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + O2 + protoaustinoid B = A + H2O + preaustinoid A;
CC Xref=Rhea:RHEA:65180, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:69023,
CC ChEBI:CHEBI:156380; Evidence={ECO:0000269|PubMed:27602587};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65181;
CC Evidence={ECO:0000269|PubMed:27602587};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:H3JQW0};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:H3JQW0};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:27602587}.
CC -!- SIMILARITY: Belongs to the FAD-binding monooxygenase family.
CC {ECO:0000305}.
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DR EMBL; LC127182; BAV69311.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1E1FFN7; -.
DR SMR; A0A1E1FFN7; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR023753; FAD/NAD-binding_dom.
DR Pfam; PF07992; Pyr_redox_2; 1.
DR SUPFAM; SSF51905; SSF51905; 2.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; NADP; Oxidoreductase.
FT CHAIN 1..641
FT /note="FAD-binding monooxygenase prhJ"
FT /id="PRO_0000449174"
FT REGION 1..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 115..118
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 125..127
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 127..128
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 133
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 272..278
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT BINDING 295..296
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
FT SITE 416
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:H3JQW0"
SQ SEQUENCE 641 AA; 71091 MW; F21E485D558925BB CRC64;
MAIGPKPESI IGSCDHPPQA EAQTGARLAA INGNNSPVSR LKDFTTDPWL TSTDQPQPGS
TTNVPYSPPD STKHARILIV GAGYGGLLFA VRLLQSGFTL EDILLVDSAG GFGGTWYWNR
YPGLMCDIES YIYMPLLEET KNIPSQKYVS GEELRTHAER IAEKWKLGAR TLFRTTVSDL
TWDDNKLQWI ATASCSSNER KQAGCTYTIN ADFAILANGT LSKPKVPDLP GIDDYTGRIF
HTARWDYDYT GGSPAIPAMD QLRTKKVGVI GTGSTAVQVI PQLARWAGEL TVFQRTPGAV
GLQINRETDH AWWRDNVQLA GPEWQRKRCE NFNAFITNPY RASLDAEDLV KDGWTKHPSF
SVALGGARNL QADFLDLAKK IDKERREIGQ QHINSTVRDP ATAEALFNPT YGWCKRPCFH
QGYFETYNRE NVRLVSTPGQ GITKLTRNGI MWGHQEFELD LIVLATGYEL GSLCPANRAR
LSIHGRGRVS MSQKWASGPA TLHGVMTRGF PNLFFPGTSQ AGVTANQSYM FDRAAEHIAY
IIQNARPRTA ASAVNPKVRI EPSLEAEELW AMETVSRAKA FAATKTCSAG SYTISARLGE
SVDESQMARH MPWGEGMASY VKILEEWRKK RDMHGLEVVY D
