AGPKS_PAEDI
ID AGPKS_PAEDI Reviewed; 1807 AA.
AC A0A411PQP9;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Atrochrysone carboxylic acid synthase Agnpks1 {ECO:0000303|PubMed:30746079};
DE Short=ACAS {ECO:0000303|PubMed:30746079};
DE EC=2.3.1.- {ECO:0000305|PubMed:30746079};
DE AltName: Full=Agnestins biosynthesis cluster protein pks1 {ECO:0000303|PubMed:30746079};
DE AltName: Full=Non-reducing polyketide synthase Agnpks1 {ECO:0000303|PubMed:30746079};
GN Name=Agnpks1 {ECO:0000303|PubMed:30746079};
OS Paecilomyces divaricatus (Penicillium divaricatum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Thermoascaceae; Paecilomyces.
OX NCBI_TaxID=644132;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP PATHWAY.
RC STRAIN=K5013;
RX PubMed=30746079; DOI=10.1039/c8sc03778g;
RA Szwalbe A.J., Williams K., Song Z., de Mattos-Shipley K., Vincent J.L.,
RA Bailey A.M., Willis C.L., Cox R.J., Simpson T.J.;
RT "Characterisation of the biosynthetic pathway to agnestins A and B reveals
RT the reductive route to chrysophanol in fungi.";
RL Chem. Sci. 10:233-238(2019).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of agnestins, dihydroxy-xanthone
CC metabolites (PubMed:30746079). The pathway begins with the assembly and
CC cyclization of atrochrysone thioester by the non-reducing polyketide
CC synthase Agnpks1 (PubMed:30746079). The atrochrysone carboxyl ACP
CC thioesterase AgnL7 then breaks the thioester bond and releases the
CC atrochrysone carboxylic acid as the first enzyme-free intermediate
CC (PubMed:30746079). The decarboxylase AgnL1 then catalyzes the concerted
CC decarboxylation-elimination required to convert atochrysone carboxylic
CC acid into emodin anthrone, which is further oxidized to emodin by the
CC anthrone oxygenase AgnL2 (PubMed:30746079). Emodin then undergoes
CC reduction catalyzed by the oxidoreductase AgnL4 to yield the
CC dihydroquinone tautomer which is the substrate for reduction by the
CC short chain dehydrogenase AgnL6 reduction to produce hydroxyketone,
CC followed by AgnL8 dehydration and likely spontaneous autoxidation to
CC chrysophanol (PubMed:30746079). Baeyer-Villiger oxidation by the
CC oxidase AgnL3 leads to monodictyphenone via cleavage of the C-10/C-10a
CC bond of chrysophanol (PubMed:30746079). Alternative cleavage at the C-
CC 4a/C-10 bond of chrysophanol leads also to the formation some cephalone
CC F (PubMed:30746079). Further conversion to agnestins A and B, requires
CC reduction to dihydro-monodictyphenone, oxidation to agnestin C probably
CC via an epoxide, and rearrangement to either agnestin A or agnestin B
CC directly, although agnestin A or agnestin B can also interconvert
CC (PubMed:30746079). Within the cluster, AgnR1 is the only unassigned
CC oxidoreductase present which could be involved in this conversion.
CC However, AgnR1 seems not to be involved in this step, and thus genes
CC involved in the proposed oxidation/reduction may be located elsewhere
CC on the genome (PubMed:30746079). Further agnestin A derivatives are
CC probably formed by spontaneous decarboxylations, dehydrations and
CC methanolysis reactions (PubMed:30746079).
CC {ECO:0000269|PubMed:30746079}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8 H(+) + holo-[ACP] + 8 malonyl-CoA = atrochrysone carboxyl-
CC [ACP] + 8 CO2 + 8 CoA + 2 H2O; Xref=Rhea:RHEA:64232, Rhea:RHEA-
CC COMP:9685, Rhea:RHEA-COMP:16552, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:64479, ChEBI:CHEBI:149712;
CC Evidence={ECO:0000305|PubMed:30746079};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64233;
CC Evidence={ECO:0000305|PubMed:30746079};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30746079}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm. {ECO:0000305|PubMed:30746079}.
CC -!- DISRUPTION PHENOTYPE: Leads to complete loss of monodictyphenone,
CC agnestins and all related compounds. {ECO:0000269|PubMed:30746079}.
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DR EMBL; MH898872; QBG38888.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A411PQP9; -.
DR SMR; A0A411PQP9; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 3: Inferred from homology;
KW Multifunctional enzyme; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..1807
FT /note="Atrochrysone carboxylic acid synthase Agnpks1"
FT /id="PRO_0000449011"
FT DOMAIN 1732..1806
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 41..173
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 414..848
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 946..1265
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1334..1653
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 584
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1766
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1807 AA; 195741 MW; 8E68629E632DACF6 CRC64;
MRYCTIPPVH SPIIRLQHGI LSKMKLIYFS NEFPPDDLHT LFRELHNHSK DRRHPILARF
LEEATLAVRE EVRRLPAHLR ALIPPFESIW NFADFADLRK GQLCGSIDGI LLCSVELGTL
IRYYENNPDA FNLETGGTIL AGLGIGLLAT AAVSLASTVA DLPITGAQVI RQAFRLGILV
DEVSQNLQPR DATDTSTPDS WAYVLPNVSA SEVQQELDTM QGIVKTPEAS KIFISALSAT
AVTISGPPAR LQAMFRTSQF FHDHKSVALP VYGGLCHAKH IYTVEDVHHI VRTSSMALLD
SKFSPQLPIH STSTGAPFPA VNATELFEHI IGEILMRAIQ WDKVIQGVAQ LAQDVGATRC
EIVVFRNSLP IHDLAAALKT IPGLETSTQE IIPWVHSKPP AGEGGPRGPL QSKIAIVGMS
CRMPGGATDT EKFWELLESG LDVHRKIPAD RFDVDSHYDP AGKRLNASHT PYGCFIDEPG
LFDAPFFNMS PREAQQTDPM QRLALVTAYE ALERAGYVAN RTAATDLHRI GTFYGQASDD
YREVNSAQEI STYFIPGGCR AFGPGRINYF FKFSGPSYSI DTACSSSLAT IQTACAALWN
GDVDTAVAGG TNVLTNSDAF AGLSHGHFLS KTPNACKTWD CNADGYCRAD AVGSIVMKRL
EDAEADNDNI LGVILAAATN HSAEAISITH PHAGHQAYLG KLVANRAGID PLDVGFVEMH
GTGTQAGDAE EIQSVTNAYA PTTRRRTAKN PLYIGAVKSN VGHSEAAAGV TAMLKVLLMF
QKNAIPPHVG IKTGLNPIFP NDLDKRQVRI PYERTEWPHV PGKKRVAVVN NFSAAGGNTT
ILLEEGPVQE ATETDPRSTH VVAVSAKSKI SLKGNIERIL AYLEQHPDAS LANLSYSTTA
RRYHHNHRVA IAASGIAQVK KQLQSALDSV DSHKPIPTTG APPVAFTFTG QGASYKSYNL
ELFSSSPYFR SQILHLDAIA QGQGFASFLP VIDGSHQRDH QHSQVMTQLA LVCTEIAIAK
YWGSLGVKPD VVIGHSLGEY AALHIAGVLS ASDTIFLVGQ RAALLEKKCK VGSHNMVAVR
ASLAQIEASA GKYPYEIACI NGPKETVLSG PTTEMDAIIP VLEGDGHKCY RLEVAFAFHS
AQTDPILDGF EALANSGVLF QAPQIPVISP LLCKVIFDDK SVNARYVRRA TREPVNFLSA
LEIARDIGIV DDETAWIEIG PHPVCVGFIK STLSPVNVAV PSLRRGDDNY TTMAQSLAAL
HCAGVKVEWS EFHRPFEAAL RLLDLPTYAW NDKTYWIQYI GDWALTKGNT FYDKEKGLNS
APAALPTPKS SISTSTVHQI IQESIDGEAG TVVMQSDLMQ ADFRAAAWGH KMNQCGVVTS
SVHADIAYTL GEYLYKKLKP KSKQVHMNIA NLEVLKGLIA NKNPESHQLI QVSVTTSDIG
SNTAELTWYN VHADGTVDEP FASATLIYGD PSEWLSSWIP MTHLVQGRIH ELERLAESGV
ANRFNHQMAY LLFANSLVDY AAKYRGMQSV VLHELEAFAD VVLSTESGGR WTVPPYFIDS
VAHLAGFVLN VSDAMDTQNN FCITPGWRSM RLARPLVAGG RYRSYVKMIP TAEDPSVYLG
DVYVLQDGVV VGMVGGIQFR RYPRILLSRF FSAPDDAHAP PVATSTSSKH AVATPATKGV
NGVKAVKAAP AVNGTNGVKT VPAVNGTNGV KATPAVNGVK PAPPVEVEVN SDTTTAKAIQ
IIAAESGLDL ADLTDDSSFA DLGVDSLMSL VIAEKFRADL GVVVGGSLFL EYPTIGDLRS
WLEEYYS
