AGN7_PAEDI
ID AGN7_PAEDI Reviewed; 314 AA.
AC A0A411PQM3;
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 carboxyl ACP thioesterase AgnL7 {ECO:0000303|PubMed:30746079};
DE Short=ACTE {ECO:0000303|PubMed:30746079};
DE EC=3.1.2.- {ECO:0000305|PubMed:30746079};
DE AltName: Full=Agnestins biosynthesis cluster protein L7 {ECO:0000303|PubMed:30746079};
GN Name=AgnL7 {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, AND 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: Atrochrysone carboxyl ACP thioesterase; part of the gene
CC cluster 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=atrochrysone carboxyl-[ACP] + H2O = atrochrysone carboxylate +
CC H(+) + holo-[ACP]; Xref=Rhea:RHEA:64236, Rhea:RHEA-COMP:9685,
CC Rhea:RHEA-COMP:16552, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:149712, ChEBI:CHEBI:149713;
CC Evidence={ECO:0000305|PubMed:30746079};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64237;
CC Evidence={ECO:0000305|PubMed:30746079};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q988B9};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q988B9};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:30746079}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC {ECO:0000305}.
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DR EMBL; MH898872; QBG38881.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A411PQM3; -.
DR SMR; A0A411PQM3; -.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF00753; Lactamase_B; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 3: Inferred from homology;
KW Hydrolase; Metal-binding; Zinc.
FT CHAIN 1..314
FT /note="Atrochrysone carboxyl ACP thioesterase AgnL7"
FT /id="PRO_0000449019"
FT ACT_SITE 107
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255"
FT BINDING 103
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 105
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 108
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
SQ SEQUENCE 314 AA; 34882 MW; 77E275F7E2D08DE2 CRC64;
MGEGGYQQIN KTLNACAFDD YLATQHARLP PLPDVEQISP RVVRVLGQNA GKFTLQGTNT
YIVGTGSRRL IIDTAQGYRA WADLIESTLA QRSIRLSHVF LTHWHGDHTK GVPDLIRMDP
DLAEGIYKNS PDHGQRPIED GQVFRVEGAT LRAVHAPGHS HDHMCFVLEE ENALFTGDNV
LGHGTSAVED LGLYMTTLRK LQAQECAVGY PAHGAVIPNL PGKITNELAQ KTRREKQCLV
ALDRIRNDQG RLASLTVSEL IDVVHGTQLD EQVRKMALEP FMDEVLRKLA EDGHVAFRVR
KGVKTWFALN TVRS
