PHNF_PENHR
ID PHNF_PENHR Reviewed; 444 AA.
AC A0A142C7A4;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-JUN-2016, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Prenyltransferase phnF {ECO:0000303|PubMed:26978228};
DE EC=2.5.1.- {ECO:0000305|PubMed:26978228};
DE AltName: Full=Phenalenone biosynthesis cluster protein F {ECO:0000303|PubMed:26978228};
GN Name=phnF {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, DISRUPTION PHENOTYPE, 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: Prenyltransferase; 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=2,3,4,7,9-pentahydroxy-6-methyl-1H-phenalen-1-one +
CC dimethylallyl diphosphate = 2,4,7,9-tetrahydroxy-6-methyl-8-(2-
CC methylbut-3-en-2-yl)-1-oxo-1H-phenalen-3-ol + diphosphate;
CC Xref=Rhea:RHEA:62656, ChEBI:CHEBI:33019, ChEBI:CHEBI:57623,
CC ChEBI:CHEBI:142788, ChEBI:CHEBI:145870;
CC Evidence={ECO:0000269|PubMed:28240554};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62657;
CC Evidence={ECO:0000269|PubMed:28240554};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:28240554}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of herqueinone, but
CC accumulates phenalenone. {ECO:0000269|PubMed:28240554}.
CC -!- SIMILARITY: Belongs to the tryptophan dimethylallyltransferase family.
CC {ECO:0000305}.
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DR EMBL; KU641631; AMP46756.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A142C7A4; -.
DR SMR; A0A142C7A4; -.
DR GO; GO:0004659; F:prenyltransferase activity; IEA:UniProt.
DR GO; GO:0009820; P:alkaloid metabolic process; IEA:InterPro.
DR GO; GO:0044249; P:cellular biosynthetic process; IEA:UniProt.
DR GO; GO:1901576; P:organic substance biosynthetic process; IEA:UniProt.
DR CDD; cd13929; PT-DMATS_CymD; 1.
DR InterPro; IPR033964; Aro_prenylTrfase.
DR InterPro; IPR017795; Aro_prenylTrfase_DMATS.
DR PANTHER; PTHR40627; PTHR40627; 1.
DR Pfam; PF11991; Trp_DMAT; 1.
DR SFLD; SFLDS00036; Aromatic_Prenyltransferase; 1.
DR TIGRFAMs; TIGR03429; arom_pren_DMATS; 1.
PE 1: Evidence at protein level;
KW Transferase.
FT CHAIN 1..444
FT /note="Prenyltransferase phnF"
FT /id="PRO_0000446164"
SQ SEQUENCE 444 AA; 50695 MW; 3F049147FF023AAB CRC64;
MSAPTQTTPV FKALTEASFS DSSLSEEAKQ NALYWWNTSA NDLARMLHQA DYSEEVQRGF
LSYYRDNICP RLGGKPDKDS ADSGVGWDGN PLEYSFELKG STKKKSVRFV VDLTELRPAD
HSNPLSMKHT QEMVDLLAEK TPNFDDTWYK VLKNWFVYAH LTPEEQTALI AKAGQQTSVI
IGFDIYPKLT SPDQLPVMGK VYFPPCYVAS DKGISRWQAV RQGIQSLPGV ESFPNILSST
EIINDYLSEK PDSWQMGTRY LATDLVSPNK ARFKVYMRCF DTSFEGIWDY YTLGGRIPNL
DEDREKFRQL MDLVSGTTYA ETRSKDDMQM GRFTSATGKL TAIYFNISPD NPYPAPKLCI
YPSNFAKDDE VIAKGLDEWL EKYGWSDDTK SMEDQVKSVF DHRKLEETTG IFTFIGIGRK
EDPTKKELSI QVYMTPELYR TPRY
