BUAC_ASPBU
ID BUAC_ASPBU Reviewed; 357 AA.
AC A0A411KZZ8;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 8.
DE RecName: Full=Trans-enoyl reductase buaC {ECO:0000303|PubMed:30735051};
DE EC=1.-.-.- {ECO:0000269|PubMed:30735051};
DE AltName: Full=Burnettramic acids biosynthesis cluster protein C {ECO:0000303|PubMed:30735051};
GN Name=buaC {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: Trans-enoyl reductase; 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 -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30735051}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; MK425157; QBE85642.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A411KZZ8; -.
DR SMR; A0A411KZZ8; -.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 3: Inferred from homology;
KW Antibiotic biosynthesis; NADP; Nucleotide-binding; Oxidoreductase.
FT CHAIN 1..357
FT /note="Trans-enoyl reductase buaC"
FT /id="PRO_0000448731"
FT BINDING 50..53
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 135..142
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 170..173
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 193..196
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 211
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 258..259
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 278..282
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 347..348
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 357 AA; 38180 MW; ACE0B22967223E48 CRC64;
MGIQHMLPST QTAIIAGPQG EFQLSHDVPV TPLADDEIIM KTAAVALNPV DTKLVGDFIT
PGAIFGFDCA GVIVAVGPKV GNGLAIGDRV CGSARGMNRE KPLGGAFAEY VMLPADLTLR
IPPAMTFAEA ASLGTALVSA CMSLFWTMQI PASLQEPAEK PFPVLVYGGS TATGTMLLQV
LKICGVRTLT TCSPKNFDLV RSYGADEVFD YNSPTCAQDI REATRNNLKY AVDCITEDST
IKICYSAIGR AGGQYIALNP YPEHLATRKV IKPGWILATL ITGEGSAWPE PYHREPDPEI
RALAKPAYSA VQKLLDEGRL RSHPIRVKDG GLAAVLDGVE VLRKGEISGQ KLVYCFN
