ID   AGN6_PAEDI              Reviewed;         268 AA.
AC   A0A411PQN6;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   08-MAY-2019, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=Short chain dehydrogenase AgnL6 {ECO:0000303|PubMed:30746079};
DE            EC=1.1.1.- {ECO:0000305|PubMed:30746079};
DE   AltName: Full=Agnestins biosynthesis cluster protein L6 {ECO:0000303|PubMed:30746079};
GN   Name=AgnL6 {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: Short chain dehydrogenase; part of the gene cluster that
CC       mediates the 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   -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC       family. {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; MH898872; QBG38882.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A411PQN6; -.
DR   SMR; A0A411PQN6; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR   InterPro; IPR002347; SDR_fam.
DR   PRINTS; PR00081; GDHRDH.
DR   PRINTS; PR00080; SDRFAMILY.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   PROSITE; PS00061; ADH_SHORT; 1.
PE   3: Inferred from homology;
KW   NAD; NADP; Oxidoreductase.
FT   CHAIN           1..268
FT                   /note="Short chain dehydrogenase AgnL6"
FT                   /id="PRO_0000449018"
FT   ACT_SITE        165
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT   BINDING         20..28
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         47..48
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         73..75
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         165..169
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         198..200
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
SQ   SEQUENCE   268 AA;  28410 MW;  159AC0167ADA4B06 CRC64;
     MGSIDTPPHL PYRLDGKVAL VTGAGRGIGA AMAVELARCG AKVIVNYARS SSFANAVVDE
     IKSLGSDAVA IQADVSQVSQ TVRLFEEAVQ VFGGLDIVCS NAGVVSFGHL SEVTEEEFDR
     VFSVNTRGQF FVAREAYRHL NSPGRIILMS SNTADSFTVP KHSLYSASKG AINTFVRCLA
     KDCGDKKITV NAVAPGGTVT DMFHETAKDY LPNADKMSKE QILQIVANVS PLTRCGYPID
     IAKVVCFLAS SESEWVNGKV LGVDGGAA