PHNG_PENHR
ID PHNG_PENHR Reviewed; 417 AA.
AC A0A142C7A5;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-JUN-2016, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Oxidoreductase phnG {ECO:0000303|PubMed:26978228};
DE EC=1.-.-.- {ECO:0000305|PubMed:26978228};
DE AltName: Full=Phenalenone biosynthesis cluster protein G {ECO:0000303|PubMed:26978228};
GN Name=phnG {ECO:0000303|PubMed:26978228};
OS Penicillium herquei.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=69774;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 10118 / CBS 336.48 / NBRC 31747 / NRRL 1040;
RX PubMed=26978228; DOI=10.1021/jacs.6b01528;
RA Gao S.S., Duan A., Xu W., Yu P., Hang L., Houk K.N., Tang Y.;
RT "Phenalenone polyketide cyclization catalyzed by fungal polyketide synthase
RT and flavin-dependent monooxygenase.";
RL J. Am. Chem. Soc. 138:4249-4259(2016).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=28240554; DOI=10.1021/jacs.7b01089;
RA Gao S.S., Garcia-Borras M., Barber J.S., Hai Y., Duan A., Garg N.K.,
RA Houk K.N., Tang Y.;
RT "Enzyme-catalyzed intramolecular enantioselective hydroalkoxylation.";
RL J. Am. Chem. Soc. 139:3639-3642(2017).
CC -!- FUNCTION: Oxidoreductase; part of the gene cluster that mediates the
CC biosynthesis of phenalenones such as herqueinone, compounds that have
CC been reported to treat tumors, bacterial infections and/or mycoses, and
CC rheumatic diseases (PubMed:26978228). The non-reducing polyketide
CC synthase phnA synthesizes the heptaketide backbone and cyclizes it into
CC the angular, hemiketal-containing naphtho-gamma-pyrone prephenalenone.
CC The product template (PT) domain of phnA catalyzes only the C4-C9 aldol
CC condensation, which is unprecedented among known PT domains
CC (PubMed:28240554, PubMed:26978228). The transformation of
CC prephenalenone to phenalenones requires an FAD-dependent monooxygenase
CC phnB, which catalyzes the C2 aromatic hydroxylation of prephenalenone
CC and ring opening of the gamma-pyrone ring simultaneously
CC (PubMed:28240554, PubMed:26978228). Subsequent intramolecular
CC deprotonation of C3 phenolic oxygen accelerates phenalenone ring
CC closure to yield the tricyclic phenalenone core with a C2 hydroxylation
CC (PubMed:28240554, PubMed:26978228). The prenyltransferase phnF further
CC catalyzes reverse C-prenylation of phenalenone by direct electrophilic
CC substitution at C6, or possibly via first a forward O-prenylation of a
CC neighboring phenol in phenalenone, followed by a Claisen rearrangement
CC (PubMed:28240554). The hydroalkoxylation enzyme phnH catalyzes the 5-
CC exo-trigcyclization via acid catalysis after the spontaneous
CC deprotonation of 7-OH, which leads to the formation of the
CC dihydrobenzofuran atrovenetin (PubMed:28240554). Atrovenetin is further
CC converted to deoxyherqueinone by the O-methyltransferase phnC which can
CC methylate C2-OH to stabilize the northern portion of the phenalenone
CC core (PubMed:28240554). Finally, the oxidoreductase phnG converts
CC deoxyherqueinone to herqueinone via C6 hydroxylation (PubMed:28240554).
CC {ECO:0000269|PubMed:26978228, ECO:0000269|PubMed:28240554}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=deoxyherqueinone + H(+) + NADPH + O2 = H2O + herqueinone +
CC NADP(+); Xref=Rhea:RHEA:62668, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:145874, ChEBI:CHEBI:145876;
CC Evidence={ECO:0000269|PubMed:28240554};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62669;
CC Evidence={ECO:0000269|PubMed:28240554};
CC -!- COFACTOR:
CC Name=6-hydroxy-FAD; Xref=ChEBI:CHEBI:60470;
CC Evidence={ECO:0000250|UniProtKB:Q9BRQ8};
CC Note=Binds 6-hydroxy-FAD non-covalently.
CC {ECO:0000250|UniProtKB:Q9BRQ8};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:28240554}.
CC -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase family.
CC {ECO:0000305}.
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DR EMBL; KU641632; AMP46757.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A142C7A5; -.
DR SMR; A0A142C7A5; -.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
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; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Oxidoreductase.
FT CHAIN 1..417
FT /note="Oxidoreductase phnG"
FT /id="PRO_0000446167"
FT BINDING 16..20
FT /ligand="6-hydroxy-FAD"
FT /ligand_id="ChEBI:CHEBI:60470"
FT /evidence="ECO:0000255"
FT BINDING 61
FT /ligand="6-hydroxy-FAD"
FT /ligand_id="ChEBI:CHEBI:60470"
FT /evidence="ECO:0000255"
FT BINDING 317
FT /ligand="6-hydroxy-FAD"
FT /ligand_id="ChEBI:CHEBI:60470"
FT /evidence="ECO:0000255"
SQ SEQUENCE 417 AA; 45024 MW; 6DA7E14C7756E31D CRC64;
MAAETATSKQ NLVILGGSYA GLSTAHYLLR HVVPQLPGKE SYQVILISAS SEAMCRPACP
RALISDDMFQ QDKLFVSIPA QFEQYLKDTF KFIHGTVTSL DHQDRCVTVS VKDGDPEKIK
CHAIVIATGA STASPLLGLN RDSETLRTNW NEFRAALPTA KHIVIAGGGP AGVETAGELG
EYLNGRAGWF HSKLENPKVE ITLVTADSKI LPILRPALAT KAEKLLNKVG VTVIKKSRVT
NVTPPGAGAE DALTANATVT LEDGKELQAD LYIPATGMTY NSSFVDASLL TDYGRVETDP
GTLRVVNGGA LLYAIGDVGS HARPAVHNIL NTVPILCANM KRDLLLAVQP DASVGEDRQF
KEDTRETQLV PVGRSKGVGA FMGFRQPGFM VWLIKGRDYW LWTTEGLWSG KHWAKGS
