PHNB_PENHR
ID PHNB_PENHR Reviewed; 409 AA.
AC A0A142C7A0;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-JUN-2016, sequence version 1.
DT 03-AUG-2022, entry version 15.
DE RecName: Full=FAD-dependent monooxygenase phnB {ECO:0000303|PubMed:26978228};
DE Short=FMO phnB;
DE EC=1.-.-.- {ECO:0000269|PubMed:26978228, ECO:0000269|PubMed:28240554};
DE AltName: Full=Phenalenone biosynthesis cluster protein B {ECO:0000303|PubMed:26978228};
GN Name=phnB {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, CATALYTIC ACTIVITY, DISRUPTION
RP PHENOTYPE, 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, 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: FAD-dependent monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of phenalenones such as herqueinone,
CC compounds that have been reported to treat tumors, bacterial infections
CC and/or mycoses, and rheumatic diseases (PubMed:26978228). The non-
CC reducing polyketide synthase phnA synthesizes the heptaketide backbone
CC and cyclizes it into the angular, hemiketal-containing naphtho-gamma-
CC pyrone prephenalenone. The product template (PT) domain of phnA
CC catalyzes only the C4-C9 aldol condensation, which is unprecedented
CC among known PT domains (PubMed:28240554, PubMed:26978228). The
CC transformation of prephenalenone to phenalenones requires an FAD-
CC dependent monooxygenase phnB, which catalyzes the C2 aromatic
CC hydroxylation of prephenalenone and ring opening of the gamma-pyrone
CC ring simultaneously (PubMed:28240554, PubMed:26978228). Subsequent
CC intramolecular deprotonation of C3 phenolic oxygen accelerates
CC phenalenone ring closure to yield the tricyclic phenalenone core with a
CC C2 hydroxylation (PubMed:28240554, PubMed:26978228). The
CC prenyltransferase phnF further catalyzes reverse C-prenylation of
CC phenalenone by direct electrophilic substitution at C6, or possibly via
CC first a forward O-prenylation of a neighboring phenol in phenalenone,
CC followed by a Claisen rearrangement (PubMed:28240554). The
CC hydroalkoxylation enzyme phnH catalyzes the 5-exo-trigcyclization via
CC acid catalysis after the spontaneous deprotonation of 7-OH, which leads
CC to the formation of the dihydrobenzofuran atrovenetin
CC (PubMed:28240554). Atrovenetin is further converted to deoxyherqueinone
CC by the O-methyltransferase phnC which can methylate C2-OH to stabilize
CC the northern portion of the phenalenone core (PubMed:28240554).
CC Finally, the oxidoreductase phnG converts deoxyherqueinone to
CC herqueinone via C6 hydroxylation (PubMed:28240554).
CC {ECO:0000269|PubMed:26978228, ECO:0000269|PubMed:28240554}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,6,7,9-tetrahydroxy-3-methyl-2,3-dihydro-1H-naphtho[2,1-
CC b]pyran-1-one + H(+) + NADPH + O2 = 2,3,4,7,9-pentahydroxy-6-methyl-
CC 1H-phenalen-1-one + 2 H2O + NADP(+); Xref=Rhea:RHEA:13461,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:142788,
CC ChEBI:CHEBI:142802; Evidence={ECO:0000269|PubMed:26978228,
CC ECO:0000269|PubMed:28240554};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13462;
CC Evidence={ECO:0000269|PubMed:26978228, ECO:0000269|PubMed:28240554};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:A6T923};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26978228, ECO:0000269|PubMed:28240554}.
CC -!- DISRUPTION PHENOTYPE: Loses the ability to produce phenalenone, and
CC accumulates prephenalenone as the predominant product.
CC {ECO:0000269|PubMed:26978228}.
CC -!- SIMILARITY: Belongs to the paxM FAD-dependent monooxygenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KU641627; AMP46752.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A142C7A0; -.
DR SMR; A0A142C7A0; -.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT CHAIN 1..409
FT /note="FAD-dependent monooxygenase phnB"
FT /id="PRO_0000446162"
FT BINDING 35..36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 36..37
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 219..221
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 235..237
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 311
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 321..329
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
FT BINDING 321..325
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:A6T923"
SQ SEQUENCE 409 AA; 44641 MW; 489228FEC969F2A5 CRC64;
MTSPQTHVIV IGAGITGLLT CQGLKKAGIS YSCFERDTSL NSRSNEWTMA IHWSLPLLAE
ILPTEVRAKL ATIACNPVAG IHSGLYPIIH GETGDLITGV PYKDGLRVPR SKMRALCAEG
IDVQYGKTLA DVAFNESGNG VVATFTDGTL VAGTMIVGAD GPRSRVRETA MGDAKLAATT
SFPIFHTNMT VCYNDAEKAK FVREKYPTSY LALSERSFHA FQSISSMPDG PDHPETWVFH
MAMAWMGQSD NAMCYAERLA LVKSKAEGLG EPARSAFMWM PEETEVHKAD ISYWISQPWN
NRDGRLTLVG DAAHPMPPYR GQGLNHCICD VSKLLAGLAG VHSGSTTLSD AIQEFEAEMI
PRGKEEVTCS VENGKMLHDW NKIQESPVFK RGFLPMDGHD TRKEIAQAS
