ID   AGN8_PAEDI              Reviewed;         174 AA.
AC   A0A411PQN4;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   08-MAY-2019, sequence version 1.
DT   03-AUG-2022, entry version 9.
DE   RecName: Full=Dehydratase AgnL8 {ECO:0000303|PubMed:30746079};
DE            EC=4.2.1.- {ECO:0000305|PubMed:30746079};
DE   AltName: Full=Agnestins biosynthesis cluster protein L8 {ECO:0000303|PubMed:30746079};
GN   Name=AgnL8 {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: Dehydratase; part of the gene cluster that mediates the
CC       biosynthesis of agnestins, dihydroxy-xanthone metabolites
CC       (PubMed:30746079). The pathway begins with the assembly and cyclization
CC       of atrochrysone thioester by the non-reducing polyketide synthase
CC       Agnpks1 (PubMed:30746079). The atrochrysone carboxyl ACP thioesterase
CC       AgnL7 then breaks the thioester bond and releases the atrochrysone
CC       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   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:30746079}.
CC   -!- SUBUNIT: Homotrimer (By similarity). Each subunit contains an active
CC       site, located in the central part of the hydrophobic core of the
CC       monomer, which functions independently (By similarity).
CC       {ECO:0000250|UniProtKB:P56221}.
CC   -!- SIMILARITY: Belongs to the scytalone dehydratase family. {ECO:0000305}.
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DR   EMBL; MH898872; QBG38880.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A411PQN4; -.
DR   SMR; A0A411PQN4; -.
DR   GO; GO:0030411; F:scytalone dehydratase activity; IEA:InterPro.
DR   GO; GO:0006582; P:melanin metabolic process; IEA:InterPro.
DR   InterPro; IPR032710; NTF2-like_dom_sf.
DR   InterPro; IPR004235; Scytalone_dehydratase.
DR   Pfam; PF02982; Scytalone_dh; 1.
DR   PIRSF; PIRSF024851; SCD1; 1.
DR   SUPFAM; SSF54427; SSF54427; 1.
PE   3: Inferred from homology;
KW   Lyase.
FT   CHAIN           1..174
FT                   /note="Dehydratase AgnL8"
FT                   /id="PRO_0000449020"
FT   ACT_SITE        79
FT                   /evidence="ECO:0000250|UniProtKB:P56221"
FT   ACT_SITE        104
FT                   /evidence="ECO:0000250|UniProtKB:P56221"
FT   BINDING         24
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P56221"
FT   BINDING         44
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P56221"
FT   BINDING         47
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P56221"
SQ   SEQUENCE   174 AA;  20200 MW;  2B3D5515C10EFA55 CRC64;
     MAKDPTFEEV TGCQRALFEW ADSYDTKDWE RLKKCVAPTL RIDYRSFLDK LWEAMPSDEF
     ILMASDPRFL GNPLLKTQHF VGLSTWQKIS PDEIEGTHQL RVPHQRYTDS NMKEVAVKGH
     AHGIATMWYK RVEDEWKFAG VCPQIRWAEF DYDKVFAEGK DHFGENGGNG EHAV