ID   PHND_PENHR              Reviewed;         131 AA.
AC   A0A142C7A2;
DT   16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT   08-JUN-2016, sequence version 1.
DT   25-MAY-2022, entry version 8.
DE   RecName: Full=Dehydratase phnD {ECO:0000303|PubMed:26978228};
DE            EC=1.-.-.- {ECO:0000305|PubMed:26978228};
DE   AltName: Full=Phenalenone biosynthesis cluster protein D {ECO:0000303|PubMed:26978228};
GN   Name=phnD {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], FUNCTION, AND PATHWAY.
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.
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: Dehydratase; 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   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:26978228}.
CC   -!- SIMILARITY: Belongs to the tpcK family. {ECO:0000305}.
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DR   EMBL; KU641629; AMP46754.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A142C7A2; -.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR011008; Dimeric_a/b-barrel.
DR   InterPro; IPR009799; EthD_dom.
DR   Pfam; PF07110; EthD; 1.
DR   SUPFAM; SSF54909; SSF54909; 1.
PE   3: Inferred from homology;
KW   Monooxygenase; Oxidoreductase.
FT   CHAIN           1..131
FT                   /note="Dehydratase phnD"
FT                   /id="PRO_0000446165"
FT   DOMAIN          13..109
FT                   /note="EthD"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   131 AA;  15212 MW;  8F6BAF6229A65CFE CRC64;
     MYAFTILGFK RDDMTEDEYH NYISTVHSAH LKALLAQNDI VSYTMQHNTS QTRDDLLNKV
     YQGQMPAEKV FECDAIIQVV FKTVEDYLRV REDPHFQTVV NPDHVNFAHP TKTRFVMGWH
     EVHVADGKVV S