PTAM_PESFW
ID PTAM_PESFW Reviewed; 540 AA.
AC A0A067XMV4; W3WSX6;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2014, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Flavin-dependent halogenase ptaM {ECO:0000303|PubMed:24302702};
DE EC=1.14.14.- {ECO:0000269|PubMed:24302702};
DE AltName: Full=Pestheic acid biosynthesis cluster protein M {ECO:0000303|PubMed:24302702};
DE Flags: Precursor;
GN Name=ptaM {ECO:0000303|PubMed:24302702}; ORFNames=PFICI_10839;
OS Pestalotiopsis fici (strain W106-1 / CGMCC3.15140).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Xylariomycetidae; Xylariales; Sporocadaceae; Pestalotiopsis.
OX NCBI_TaxID=1229662;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND INDUCTION.
RC STRAIN=W106-1 / CGMCC3.15140;
RX PubMed=24302702; DOI=10.1002/cbic.201300626;
RA Xu X., Liu L., Zhang F., Wang W., Li J., Guo L., Che Y., Liu G.;
RT "Identification of the first diphenyl ether gene cluster for pestheic acid
RT biosynthesis in plant endophyte Pestalotiopsis fici.";
RL ChemBioChem 15:284-292(2014).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND INDUCTION.
RC STRAIN=W106-1 / CGMCC3.15140;
RX PubMed=25623211; DOI=10.1186/s12864-014-1190-9;
RA Wang X., Zhang X., Liu L., Xiang M., Wang W., Sun X., Che Y., Guo L.,
RA Liu G., Guo L., Wang C., Yin W.B., Stadler M., Zhang X., Liu X.;
RT "Genomic and transcriptomic analysis of the endophytic fungus
RT Pestalotiopsis fici reveals its lifestyle and high potential for synthesis
RT of natural products.";
RL BMC Genomics 16:28-28(2015).
CC -!- FUNCTION: Flavin-dependent halogenase; part of the gene cluster that
CC mediates the biosynthesis of pestheic acid, a diphenyl ether which is a
CC biosynthetic precursor of the unique chloropupukeananes
CC (PubMed:24302702). The biosynthesis initiates from condensation of
CC acetate and malonate units catalyzed by the non-reducing PKS ptaA
CC (PubMed:24302702). As the ptaA protein is TE/CLC domain-deficient,
CC hydrolysis and Claisen cyclization of the polyketide could be catalyzed
CC by ptaB containing a beta-lactamase domain (PubMed:24302702). The ptaB
CC protein might hydrolyze the thioester bond between the ACP of ptaA and
CC the intermediate to release atrochrysone carboxylic acid, which is
CC spontaneously dehydrated to form endocrocin anthrone (PubMed:24302702).
CC Endocrocin anthrone is then converted to endocrocin, catalyzed by the
CC anthrone oxygenase ptaC (PubMed:24302702). Spontaneous decarboxylation
CC of endocrocin occurs to generate emodin (PubMed:24302702). An O-
CC methyltransferase (ptaH or ptaI) could methylate emodin to form
CC physcion (PubMed:24302702). PtaJ could then catalyze the oxidative
CC cleavage of physcion, and rotation of the intermediate could then
CC afford desmethylisosulochrin (PubMed:24302702). PtaF, a putative NADH-
CC dependent oxidoreductase, might also participate in the oxidative
CC cleavage step (PubMed:24302702). Desmethylisosulochrin is then
CC transformed by another O-methyltransferase (ptaH or ptaI) to form
CC isosulochrin (PubMed:24302702). Chlorination of isosulochrin by ptaM in
CC the cyclohexadienone B ring then produces chloroisosulochrin
CC (PubMed:24302702). PtaE is responsible for the oxidative coupling
CC reactions of both benzophenones isosulochrin and chloroisosulochrin to
CC RES-1214-1 and pestheic acid respectively, regardless of chlorination.
CC {ECO:0000269|PubMed:24302702}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P95480};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P95480};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=155 uM for isosulochrin {ECO:0000269|PubMed:24302702};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:24302702}.
CC -!- INDUCTION: The cluster is expressed in rice fermentation medium
CC (PubMed:25623211). Expression is correlated with the production of
CC pestheic acid (PubMed:24302702). Three regulators are located in the
CC cluster (ptaR1, ptaR2 and ptaR3), suggesting that the production of
CC pestheic acid is controlled by a complex regulatory mechanism
CC (PubMed:24302702). {ECO:0000269|PubMed:24302702,
CC ECO:0000269|PubMed:25623211}.
CC -!- DISRUPTION PHENOTYPE: Abolishes completely the production of
CC chloroisosulochrin and pestheic acid, whereas their non-chlorinated
CC precursors, isosulochrin and RES-1214-1, still accumulate
CC (PubMed:24302702). {ECO:0000269|PubMed:24302702}.
CC -!- SIMILARITY: Belongs to the flavin-dependent halogenase 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; KC145148; AGO59046.1; -; Genomic_DNA.
DR EMBL; KI912116; ETS76965.1; -; Genomic_DNA.
DR RefSeq; XP_007837611.1; XM_007839420.1.
DR AlphaFoldDB; A0A067XMV4; -.
DR SMR; A0A067XMV4; -.
DR STRING; 1229662.A0A067XMV4; -.
DR EnsemblFungi; ETS76965; ETS76965; PFICI_10839.
DR GeneID; 19275852; -.
DR KEGG; pfy:PFICI_10839; -.
DR eggNOG; ENOG502QW6Y; Eukaryota.
DR OMA; ASINGDC; -.
DR OrthoDB; 462247at2759; -.
DR Proteomes; UP000030651; Unassembled WGS sequence.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR006905; Flavin_halogenase.
DR Pfam; PF04820; Trp_halogenase; 2.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Glycoprotein; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..540
FT /note="Flavin-dependent halogenase ptaM"
FT /id="PRO_0000443043"
FT BINDING 14..17
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 37..48
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 330..331
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT CARBOHYD 159
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 243
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 523
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 540 AA; 60041 MW; 635E3B018EDDA296 CRC64;
MSVPAQTSVL IVGGGPAGSY AATVLAREGV DVVLLEAEKF PRYHIGESML ASIRFFLRFV
ELEEEFDRHG FEKKYGATFK ITEKNPAYTD FAASLGEGGY SWNVVRSESD EIIFRYAGKC
GAKTFDGTKV ESLTFEPYPH EGFDESVHLA NPGRPVSANW SRKDGSSGVI KFDYIIDGSG
RNGLISTKYL KNRSFNQGLK NIANWTYWKG AKRFNVGEKN ENSPLFEALK DGSGWVWAIP
LHNDTISVGV VARQDAFFEK KKESGLSGEA FYKEYLKLAP QIKNELLRDA TIVSDIKQAT
DWSYSASAYA GPNFRLIGDA GCFVDPYFSS GCHLAMTSAL SASVSIQAVR RGQCDELTGA
KWHTTKVAEG YTRFLLLVMT VQRQLRMKDK NIISTDEEEG FDMAFKKIQP VIQGVADTRT
EDEQTQRRAA EAVDFSLESF EITPEKQAAV ISKIERSQAE PELLEKLTPE EVHILGNIVN
RTFEREKDEL NLTHFTGDMI DGYSAKLEHG NIGLYKREKA LLNGTASRAA AVLKSIHQVA
