ID   DMPKS_CRYX8             Reviewed;        1781 AA.
AC   A0A4P8DJU2;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   31-JUL-2019, sequence version 1.
DT   03-AUG-2022, entry version 9.
DE   RecName: Full=Atrochrysone carboxylic acid synthase {ECO:0000250|UniProtKB:Q5BH30};
DE            Short=ACAS {ECO:0000250|UniProtKB:Q5BH30};
DE            EC=2.3.1.- {ECO:0000250|UniProtKB:Q5BH30};
DE   AltName: Full=Dimeric xanthone biosynthesis cluster PKS {ECO:0000303|PubMed:30996871};
DE   AltName: Full=Non-reducing polyketide synthase dmx-nrPKS {ECO:0000303|PubMed:30996871};
GN   Name=dmx-nrPKS {ECO:0000303|PubMed:30996871};
OS   Cryptosporiopsis sp. (strain 8999).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Leotiomycetes;
OC   Helotiales; Dermateaceae; Cryptosporiopsis; unclassified Cryptosporiopsis.
OX   NCBI_TaxID=2572248;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=8999;
RX   PubMed=30996871; DOI=10.1039/c8sc05126g;
RA   Greco C., de Mattos-Shipley K., Bailey A.M., Mulholland N.P., Vincent J.L.,
RA   Willis C.L., Cox R.J., Simpson T.J.;
RT   "Structure revision of cryptosporioptides and determination of the genetic
RT   basis for dimeric xanthone biosynthesis in fungi.";
RL   Chem. Sci. 10:2930-2939(2019).
CC   -!- FUNCTION: Atrochrysone carboxylic acid synthase; part of the gene
CC       cluster that mediates the biosynthesis of the dimeric xanthones
CC       cryptosporioptides (PubMed:30996871). The pathway begins with the
CC       synthesis of atrochrysone thioester by the polyketide synthase dmx-
CC       nrPKS (Probable). The atrochrysone carboxyl ACP thioesterase dmxR1 then
CC       breaks the thioester bond and releases the atrochrysone carboxylic acid
CC       from dmx-nrPKS (Probable). Atrochrysone carboxylic acid is
CC       decarboxylated by the decarboxylase dmxR15, and oxidized by the
CC       anthrone oxygenase dmxR16 to yield emodin (Probable). Emodin is then
CC       reduced to emodin hydroquinone by the oxidoreductase dmxR7 (Probable).
CC       A-ring reduction by the short chain dehydrogenase dmxR18, dehydration
CC       by the scytalone dehydratase-like protein dmxR17 and probable
CC       spontaneous re-oxidation, results in overall deoxygenation to
CC       chrysophanol (PubMed:30996871). Baeyer-Villiger oxidation by the
CC       Baeyer-Villiger monooxygenase (BVMO) dmxR6 then yields monodictylactone
CC       in equilibrium with monodictyphenone (PubMed:30996871). In the case of
CC       the cryptosporioptides biosynthesis, monodictylactone is reduced at C-
CC       12 to an alcohol (by the short chain dehydrogenases dmxR12 or dmxR8)
CC       and hydroxylated at C-5 by dmxR9, yielding the electron-rich aromatic
CC       which could eliminate H(2)O to form the ortho-quinonemethide, followed
CC       by tautomerisation to paraquinone and complete the formal reduction to
CC       produce the 10-methylgroup (Probable). Conjugate addition of C-4a-OH to
CC       the resulting paraquinone by the monooxygenase dmxR10 then gives
CC       cyclohexadienone, which is then reduced at C-5 by the short chain
CC       dehydrogenase dmxR3 to give the dihydroxanthone (Probable). The 6,7-
CC       epoxide in the cryptosporioptides could be introduced by the cytochrome
CC       P450 monooxygenase dmxL3 (Probable). The highly reducing PKS dmxL2
CC       manufactures butyrate, which is further carboxylated by dmxL1 to form
CC       ethylmalonate (PubMed:30996871). It is not yet clear whether the
CC       carboxylation occurs while the butyrate is attached to the ACP of
CC       dmxL2, but this unusual fungal metabolite could then be esterified to
CC       O-5 by the O-acetyltransferase dmxR13 (PubMed:30996871). Finally,
CC       dimerization performed by dmxR5 gives the observed dimers
CC       cryptosporioptides A, B and C as the final products of the pathway
CC       (PubMed:30996871). {ECO:0000269|PubMed:30996871,
CC       ECO:0000305|PubMed:30996871}.
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:0000250|UniProtKB:Q5BH30};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64233;
CC         Evidence={ECO:0000250|UniProtKB:Q5BH30};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:30996871}.
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:0000250|UniProtKB:Q5B0D0}.
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DR   EMBL; MK182094; QCL09091.1; -; Genomic_DNA.
DR   SMR; A0A4P8DJU2; -.
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; -; 2.
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..1781
FT                   /note="Atrochrysone carboxylic acid synthase"
FT                   /id="PRO_0000453430"
FT   DOMAIN          1703..1780
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          15..253
FT                   /note="N-terminal acylcarrier protein transacylase domain
FT                   (SAT)"
FT                   /evidence="ECO:0000255"
FT   REGION          393..826
FT                   /note="Ketosynthase (KS) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          925..1244
FT                   /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1312..1631
FT                   /note="Product template (PT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1633..1653
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        563
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   MOD_RES         1740
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1781 AA;  193642 MW;  B68C6CD27010187C CRC64;
     MKVAYFSNEF PHDDTRDLFR RLHVHSKDKR YPTLARFISE ATSALRDEVA ALPTALRALV
     PTFDSIFSLV DNTAVRQGRL GGAIDGVLLC ALHIATFIGF YESDTEEEFD LSAVDTCLAG
     LGTGLLSTVA LSLSPSLADL PTTGALVVGI AFRLGVVVDD VSQNLQPRPA IAESGPGDSW
     AYVVPDVSPE EIQKELDTIQ IAEKTPEPSK IFISALSRTS VTVSGPPARL KHLFLVSAYF
     RDRKHVALPV YAGLCHAAHI YDEHHVEKII QSSSLDSISA KYRPRVRVLS TSTGRPFSGL
     TAKELFRNVI EEILTKSIEW DEVIRGIIQR AKDSAAVECD VLIFRTSLPV HELLATFGTE
     LQQFRASTKD LVSWIAKPDS PPAKPSGKAQ SKIAIVGMAC RLPGGSTDPD KFWDLLEKGL
     DVHRKIPADR FDVDSHYDPE GKRMNASWTP YGCFIDEPGL FDAPFFNMSP REALQTDPMQ
     RLALVTAYEA LEKAGVVPNR TAATDAHRIG TYYGQASDDY REVNTAQEIS TYFITGGCRA
     FGPGRINYFF KFSGPSYSVD TACSSGLAAI QACTSLWAGE VETAIAGGVN VLTNCDAFAG
     LSNGHFLTKT PNACKTWDCD ADGYCRADGV VSLVLKRLED AEADNDNILG VILGAGTNHS
     ADAVSITHPH AGAQAFLTSQ TVRKAGVDPF DISYIEMHGT GTQAGDAQEI LSVTEVFAPL
     TRRRTSKQPL YIGSVKANVG HGEAVSGPTA LVKLLLMFQK EAIPAHVGIK NSINPGFPKD
     LAKRNLHIPY EQTPWPRVPG KKRIAVVNNF SAAGGNTSVV VEEASVREPV KGTDPRSSHL
     ITVSAKSKVS LKGNLERLIA YVEANPDVSL ADLAYTTTAR RRHHNHRVAV AASDAAQLKK
     QLGSYLQSVE SHKPIPSTGQ PPVVFAFTGQ GASHPSMNLE LFHHSPYFRA QLLHLDSLAQ
     QQGFGSFIPV VDGSHERSHA HSPTATQLAL VCVEIALAKY WESLGVKPDV VIGHSLGEYA
     ALHVAGVLSA SDAISMVGRR AALLEQKCQT GSHQMLAVRA SLADIQAIVH DKPYEVSCIN
     GPRDTVLSGT REQVAVLTEV LQAAGHRCIS LDVAFAFHSA QTDPILEEFE EVTKSSILFQ
     PPNLPIISPL LGKVIFDEKT VNATYVRRAT REAVNFLGAI EIAQQMSTID ETMAWIEIGP
     HPVCINFVKS ILPRVNVAVP SIRRGEDNWQ TVSHSLGLLH CAGLELNWNE FHLAFEENLR
     LVDLPTYAWN DKTHWIQYIG DWALTKGNTF YDAEKAAANP GALVHTRSNI KTSTVQQIIE
     ETFSDSAATV VMQSNLMEPD FLAAAHGHRM NDCGVVTSSI HADIAYTLGA YIMKKLRPKS
     QNVGMDIANL EVLKGLIAQK NTDKPQFIQV SAQVHDIDLG VAHLQWHNVS SNGEVDEPFA
     SADIVYGLPT DWLKSWVPAT HLVQGRIEAL ERLAEAGIAN RLSHNMAYLL FANNLVDYAQ
     KYRGMQSVVM HELEAFADVT LTTEKGGVWT VPPYFIDSVA HLAGFVMNVS DANDTKQNFC
     VTPGWGSMRF AKPLVAGQKY RSYVKMIPTE EDPTVYLGDV YVLQDGVIIG EVGAIKFRRY
     PRVLLNRFFS APDSDTSKHT SATDVSPPKK VVQSASTTTT VTKALPSKPV AIPAPQVAAP
     VVQPTEQVTV VKAVTELTST VEVDSDSTAS KAMALVAAEG GLELSDLPDD ANFANLGVDS
     LMSLVIAEKF REQLGVTVNG SLFLEYPTVG DLKAWLMEYY S