ID   BUAE_ASPBU              Reviewed;         319 AA.
AC   A0A411L030;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   08-MAY-2019, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=Proline hydroxylase buaE {ECO:0000303|PubMed:30735051};
DE            EC=1.14.11.- {ECO:0000255|PROSITE-ProRule:PRU00805, ECO:0000269|PubMed:30735051};
DE   AltName: Full=2-oxoglutarate-dependent dioxygenase buaE;
DE   AltName: Full=Burnettramic acids biosynthesis cluster protein E {ECO:0000303|PubMed:30735051};
GN   Name=buaE {ECO:0000303|PubMed:30735051};
OS   Aspergillus burnettii.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX   NCBI_TaxID=2508778;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC   STRAIN=FRR 5400;
RX   PubMed=30735051; DOI=10.1021/acs.orglett.8b04042;
RA   Li H., Gilchrist C.L.M., Lacey H.J., Crombie A., Vuong D., Pitt J.I.,
RA   Lacey E., Chooi Y.H., Piggott A.M.;
RT   "Discovery and Heterologous Biosynthesis of the Burnettramic Acids: Rare
RT   PKS-NRPS-Derived Bolaamphiphilic Pyrrolizidinediones from an Australian
RT   Fungus, Aspergillus burnettii.";
RL   Org. Lett. 21:1287-1291(2019).
CC   -!- FUNCTION: Proline hydroxylase; part of the gene cluster that mediates
CC       the biosynthesis of burnettramic acids, an unusual class of
CC       bolaamphiphilic pyrrolizidinediones that display potent antibacterial,
CC       antifungal, and cytotoxic activities (PubMed:30735051). The first step
CC       of the biosynthesis of burnettramic acids is the hydroxylation of
CC       proline by the proline hydroxylase buaE to generate 4-hydroxyproline
CC       (PubMed:30735051). The PKS-NRPS buaA and trans-enoyl reductase buaC
CC       construct the highly reduced polyketide chain, and the condensation (C)
CC       domain of buaA then catalyzes the amide bond formation with the
CC       activated 4-hydroxyproline (PubMed:30735051). This is followed by the R
CC       domain releasing the nascent polyketide-peptide directly via a
CC       Dieckmann condensation to afford a tetramic acid fused to the
CC       hydroxyproline, generating the bicyclic pyrrolidinedione moiety
CC       (PubMed:30735051). The cytochrome P450 monooxygenases buaD and buaG are
CC       likely responsible for the multiple hydroxylations on the polyketide
CC       chain and its terminus, although in the heterologous context, buaD does
CC       not appear to be required. Therefore, while buaG may be a
CC       multifunctional cytochrome P450 monooxygenase, it cannot be ruled out
CC       that the two secondary alcohols on the polyketide chain could have an
CC       acetate origin (PubMed:30735051). Finally, the glycosyltransferase buaB
CC       transfers beta-D-mannose to the aglycone burnettramic acid A to form
CC       burnettramic acid A (PubMed:30735051). Burnettramic acid B is a minor
CC       cis-pyrrolizidine epimer of burnettramic acid A and it is likely that
CC       small amounts of it form naturally in acidic environments
CC       (PubMed:30735051). {ECO:0000269|PubMed:30735051}.
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: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30735051}.
CC   -!- SIMILARITY: Belongs to the iron/ascorbate-dependent oxidoreductase
CC       family. {ECO:0000305}.
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DR   EMBL; MK425157; QBE85645.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A411L030; -.
DR   SMR; A0A411L030; -.
DR   GO; GO:0051213; F:dioxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; 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   3: Inferred from homology;
KW   Antibiotic biosynthesis; Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT   CHAIN           1..319
FT                   /note="Proline hydroxylase buaE"
FT                   /id="PRO_0000448733"
FT   DOMAIN          168..280
FT                   /note="Fe2OG dioxygenase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT   BINDING         195
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT   BINDING         197
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT   BINDING         255
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT   BINDING         271
FT                   /ligand="2-oxoglutarate"
FT                   /ligand_id="ChEBI:CHEBI:16810"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
SQ   SEQUENCE   319 AA;  36238 MW;  071B733974FCB933 CRC64;
     MEVERLDYTD FLNEAPGRQE AFVQHLYAAL SRVGFAKITN HPIPESVILQ LFAWTKGFFT
     LPLEHKRKAA HPPQPNPHRG WSCIGQEKLS VIAQGKAVLD LKESFDMGPG DDELYPNIWT
     DEGDLPGFRA FMEDFYGRCQ SLHLQLLSAI ARSMQLPDSY FAPLCSQNSS ELRLNHYPAV
     SRHDLTTGTM RISSHTDFGT ITLLFQDSVG GLEVEDQTRP GHYMPVAADD CTDIIVNVGD
     CLQRWTNDRL RSANHRVTLP RGLTHGMVDD RYSIAYFGKP SRDVSVRTLS ALLRANEEAK
     YREEMTAWQY NQSRLLQTY