PHNC_PENHR
ID PHNC_PENHR Reviewed; 429 AA.
AC A0A142C7A1;
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=O-methyltransferase phnC {ECO:0000303|PubMed:26978228};
DE EC=2.1.1.- {ECO:0000255|PROSITE-ProRule:PRU01020};
DE AltName: Full=Phenalenone biosynthesis cluster protein C {ECO:0000303|PubMed:26978228};
GN Name=phnC {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 DISRUPTION PHENOTYPE.
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: O-methyltransferase; part of the gene cluster that mediates
CC the biosynthesis of phenalenones such as herqueinone, compounds that
CC have been reported to treat tumors, bacterial infections and/or
CC mycoses, and rheumatic diseases (PubMed:26978228). The non-reducing
CC polyketide synthase phnA synthesizes the heptaketide backbone and
CC cyclizes it into the angular, hemiketal-containing naphtho-gamma-pyrone
CC prephenalenone. The product template (PT) domain of phnA catalyzes only
CC the C4-C9 aldol condensation, which is unprecedented among known PT
CC domains (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'R)-atrovenetin + S-adenosyl-L-methionine = deoxyherqueinone
CC + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:62664,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:145872, ChEBI:CHEBI:145874;
CC Evidence={ECO:0000269|PubMed:28240554};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62665;
CC Evidence={ECO:0000269|PubMed:28240554};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:28240554}.
CC -!- DISRUPTION PHENOTYPE: Leads to decreased, but does not abolish,
CC production of herqueinone. {ECO:0000269|PubMed:26978228}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family. COMT
CC subfamily. {ECO:0000305}.
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DR EMBL; KU641628; AMP46753.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A142C7A1; -.
DR SMR; A0A142C7A1; -.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..429
FT /note="O-methyltransferase phnC"
FT /id="PRO_0000446163"
FT BINDING 285
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
SQ SEQUENCE 429 AA; 48082 MW; 2E57BAEC279EEE0A CRC64;
MDQNTLIKTA QQILDTTTEL SKHLAESDIA IPNDLNVGTT SGLWTTHNAE IEALRLKITG
LSQNLGMLLE GPHGFLHEYV SVNWEHGALY TLLDHNVLEQ IPLDGSKIAI ADLATRVGLP
ADKLLRICRL VATVGIIRED TEGEFSHTAI SETLVKDQGY KSFIGFQTFE TRVASAHLAD
SLRKPNPYWN EGQAAFELAW GMPMYDWHRE HPEKGKRFAQ AMQSVSKNLD AGNDMIIQWV
KGSEGLQNGK PLHVVEIQGK TGAFSAELAT LYPNAEFEVQ DTSADLISRG KQTLDPELAS
RVKFSQRDLF AVRKCDEVSD FTDNTVVFLL RGVLWNHSDE EVITLLRSFL PAMEHGIKPI
VLISDLVSPI WATFESHVER AFRRRDVTLT TMHNVKQRTS TEWSQLLQSA DPNFKVCAFP
VDLFGIFEN
