ID   EFUE_HORCR              Reviewed;         400 AA.
AC   A0A2Z4HPZ6;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   10-OCT-2018, sequence version 1.
DT   03-AUG-2022, entry version 9.
DE   RecName: Full=Dehydrogenase efuE {ECO:0000303|PubMed:30051576};
DE            EC=1.-.-.- {ECO:0000305|PubMed:30051576};
DE   AltName: Full=Enfumafungin biosynthesis cluster protein E {ECO:0000303|PubMed:30051576};
GN   Name=efuE {ECO:0000303|PubMed:30051576};
OS   Hormonema carpetanum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC   Dothideomycetidae; Dothideales; Dothioraceae; Hormonema.
OX   NCBI_TaxID=284138;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RX   PubMed=30051576; DOI=10.1111/1462-2920.14333;
RA   Kuhnert E., Li Y., Lan N., Yue Q., Chen L., Cox R.J., An Z., Yokoyama K.,
RA   Bills G.F.;
RT   "Enfumafungin synthase represents a novel lineage of fungal triterpene
RT   cyclases.";
RL   Environ. Microbiol. 20:3325-3342(2018).
CC   -!- FUNCTION: Dehydrogenase; part of the gene cluster that mediates the
CC       biosynthesis of enfumafungin, a glycosylated fernene-type triterpenoid
CC       with potent antifungal activity, mediated by its interaction with beta-
CC       1,3-glucan synthase and the fungal cell wall (PubMed:30051576). The
CC       pathway begins with the terpene cyclase-glycosyl transferase fusion
CC       protein that most likely uses 2,3-oxidosqualene as substrate and
CC       catalyzes glycosylation immediately after cyclization (Probable). The
CC       fernene glycoside then could be processed by the desaturase efuI which
CC       catalyzes isomerization of a double bond established by efuA to form
CC       the core structure (Probable). The latter would then undergo a series
CC       of hydroxylations in unknown order at C-2, C-19, C-23 and C-25, which
CC       would be catalyzed by two of the three cytochrome P450 monooxygenases
CC       efuB, efuG or efuH (Probable). The hydroxy-group at C-25 becomes
CC       oxidized by the dehydrogenase efuE to enable a spontaneous, non-
CC       enzymatic hemiacetal formation with C-23 (Probable). After
CC       hydroxylation at C-2, acetylation by the acetyltransferase efuC takes
CC       place (Probable). The final steps in enfumafungin biosynthesis require
CC       expansion of the 5-membered ring by lactonization via a Baeyer-Villiger
CC       reaction mediated by one of the BGC's cytochrome P450 monooxygenases
CC       (efuB, efuG or efuH) followed by ring cleavage (Probable). This type of
CC       reaction would establish a double bond between C-20 and C-21 which
CC       could be reduced by the reductase efuL to form the final product
CC       (Probable). {ECO:0000269|PubMed:30051576, ECO:0000305|PubMed:30051576}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000305|PubMed:30051576}.
CC   -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC       dehydrogenase family. {ECO:0000305}.
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DR   EMBL; MF611886; AWW17214.1; -; Genomic_DNA.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR   GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR   InterPro; IPR029753; D-isomer_DH_CS.
DR   InterPro; IPR029752; D-isomer_DH_CS1.
DR   InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   Pfam; PF00389; 2-Hacid_dh; 1.
DR   Pfam; PF02826; 2-Hacid_dh_C; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
DR   PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE   3: Inferred from homology;
KW   NAD; Oxidoreductase.
FT   CHAIN           1..400
FT                   /note="Dehydrogenase efuE"
FT                   /id="PRO_0000454462"
FT   ACT_SITE        305
FT                   /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT   ACT_SITE        334
FT                   /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT   ACT_SITE        352
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT   BINDING         222..223
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT   BINDING         303..305
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT   BINDING         329
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q9I3W9"
FT   BINDING         352..355
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q9I3W9"
SQ   SEQUENCE   400 AA;  43876 MW;  E16FBBF5FC9541E5 CRC64;
     MVESSRWYSV PETLSAKAGL PIVSLPFNNQ IQTSPFSVRS SYYLPLQTVN MSPSLVAPRQ
     KALSLRHPTM AGKEYLEEFS KKYIIDVLDV PNREEWLKQL PKKVAKDGPY SALIIGMGTG
     PYEPFDAEFC QALLPDLKLV VSASAGYNEF DVSWMTENNI WFCNTVDAVS EATADMAIFL
     TLAALRDTTN AERSARAGNW KAGFVPCRDP TGLRLGIIGM GAIGKHIARK AAVFNLEIVY
     HNRKRLQEAD ETTYKATYCP TLASLLETSD IVSISVPLND ETTGMISESE IALMKDSSIL
     INTARGAVVD EAALIEALES GKIWRAGLDV FCNEPDINPY FKTSDKVVVQ PHLGGLTAVA
     FRKAYRECFE NVASFFDTGK PLAPVNDVTR AKGTPTASLP