ID   HTYE_ASPRU              Reviewed;         329 AA.
AC   K0DZA0;
DT   25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT   28-NOV-2012, sequence version 1.
DT   03-AUG-2022, entry version 27.
DE   RecName: Full=2-oxoglutarate-dependent dioxygenase htyE {ECO:0000303|PubMed:22998630};
DE            EC=1.14.-.- {ECO:0000305|PubMed:22998630};
DE   AltName: Full=L-homotyrosine biosynthetic cluster protein E {ECO:0000303|PubMed:22998630};
GN   Name=htyE {ECO:0000303|PubMed:22998630};
OS   Aspergillus rugulosus (Emericella rugulosa).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=41736;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PATHWAY, AND BIOTECHNOLOGY.
RC   STRAIN=ATCC 58397 / NRRL 11440;
RX   PubMed=22998630; DOI=10.1021/ja307220z;
RA   Cacho R.A., Jiang W., Chooi Y.H., Walsh C.T., Tang Y.;
RT   "Identification and characterization of the echinocandin B biosynthetic
RT   gene cluster from Emericella rugulosa NRRL 11440.";
RL   J. Am. Chem. Soc. 134:16781-16790(2012).
RN   [2]
RP   FUNCTION, AND PATHWAY.
RX   PubMed=29352089; DOI=10.1128/aem.02370-17;
RA   Mattay J., Houwaart S., Huettel W.;
RT   "Cryptic production of trans-3-hydroxyproline in echinocandin B
RT   biosynthesis.";
RL   Appl. Environ. Microbiol. 0:0-0(2018).
CC   -!- FUNCTION: 2-oxoglutarate-dependent dioxygenase; part of the gene
CC       cluster that mediates the de novo generation of L-homotyrosine from
CC       acetyl-CoA and 4-hydroxyphenyl-pyruvate (PubMed:22998630). L-
CC       homotyrosine is a building block of echinocandin B, a fungal lipidated
CC       cyclic hexapeptide that acts as an antifungal agent (PubMed:22998630).
CC       L-homotyrosine 4-hydroxyphenyl-pyruvate first undergoes an aldol-type
CC       condensation by htyA with the C-2 of acetyl-CoA followed by the release
CC       of CoA to form 2-(4-hydroxybenzyl)-malate (PubMed:22998630). This is
CC       followed by isomerization of 2-(4-hydroxy-benzyl)-malate to 3-(4-
CC       hydroxybenzyl)-malate by htyD (PubMed:22998630). Thereafter, 3-(4-
CC       hydroxybenzyl)-malate undergoes decarboxylation and oxidation to form
CC       2-oxo-4-(4-hydroxybenzyl)butanoic acid, coupled to reduction of NAD(+)
CC       to NADH by htyC (PubMed:22998630). The product then undergoes
CC       transamination catalyzed by htyB to form L-homotyrosine
CC       (PubMed:22998630). {ECO:0000269|PubMed:22998630}.
CC   -!- COFACTOR:
CC       Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00805};
CC       Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC       ProRule:PRU00805};
CC   -!- PATHWAY: Antifungal biosynthesis. {ECO:0000269|PubMed:29352089,
CC       ECO:0000305|PubMed:22998630}.
CC   -!- BIOTECHNOLOGY: Due to their effectiveness as antifungal agents,
CC       echinocandin derivatives can be used for the treatment of human
CC       invasive candidiasis (PubMed:22998630). {ECO:0000269|PubMed:22998630}.
CC   -!- SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase
CC       family. {ECO:0000305}.
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DR   EMBL; JX421685; AFT91391.1; -; Genomic_DNA.
DR   AlphaFoldDB; K0DZA0; -.
DR   SMR; K0DZA0; -.
DR   GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.120.330; -; 1.
DR   InterPro; IPR026992; DIOX_N.
DR   InterPro; IPR044861; IPNS-like_FE2OG_OXY.
DR   InterPro; IPR027443; IPNS-like_sf.
DR   InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR   Pfam; PF03171; 2OG-FeII_Oxy; 1.
DR   Pfam; PF14226; DIOX_N; 1.
DR   PROSITE; PS51471; FE2OG_OXY; 1.
PE   1: Evidence at protein level;
KW   Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT   CHAIN           1..329
FT                   /note="2-oxoglutarate-dependent dioxygenase htyE"
FT                   /id="PRO_0000443844"
FT   DOMAIN          175..289
FT                   /note="Fe2OG dioxygenase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT   BINDING         201
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT   BINDING         203
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT   BINDING         261
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT   BINDING         280
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
SQ   SEQUENCE   329 AA;  37699 MW;  A36918ECEE1D19F9 CRC64;
     MAITTLDFNQ FRSTSADERQ IFCADLCETL SVYGFAKIRN TTLSNELIDE IFKYTRSFFA
     LPNDIKAKAK HPNAPNPHRG WSAIGQERVW KISGFEQNKE RTDSYNEFRE SFDQGAADDQ
     LFPNRWVDED DLPGFQAFME GFYKSCDELH AHLLRAISTG LKLPDTLLPS KHRHNTSELR
     LLHYPPIPCS ALRSNMRIGE HSDFGTLTLL LQDSVGGLQV EDQRNPRSFI PVEPEDGYEV
     VINIGDCLQR WTNRRLCSAN HRVMLPEGKD VDSEEVLDDR YSVAYFGKPD RDVLVDTLPE
     CVEVGERVEY GDHLTALQYN QIKLTRTYG