BUAG_ASPBU
ID BUAG_ASPBU Reviewed; 503 AA.
AC A0A411KZZ4;
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=Cytochrome P450 monooxygenase buaG {ECO:0000303|PubMed:30735051};
DE EC=1.-.-.- {ECO:0000269|PubMed:30735051};
DE AltName: Full=Burnettramic acids biosynthesis cluster protein G {ECO:0000303|PubMed:30735051};
DE Flags: Precursor;
GN Name=buaG {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: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates 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=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30735051}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MK425157; QBE85647.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A411KZZ4; -.
DR SMR; A0A411KZZ4; -.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002974; Cyt_P450_E_CYP52.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR01239; EP450IICYP52.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Antibiotic biosynthesis; Glycoprotein; Heme; Iron; Metal-binding;
KW Monooxygenase; Oxidoreductase; Signal.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..503
FT /note="Cytochrome P450 monooxygenase buaG"
FT /id="PRO_5019205234"
FT BINDING 448
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 393
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 503 AA; 56395 MW; A7E360BAEA259EE9 CRC64;
MFLLILYAFL TAVVARKLSA AVSVYRYRKM HGLLLARPLN QKGDVIGFSL FRGMQKSARE
GLSLQRHYEN TQQHGPTISA VLLGKSFIST SDPENIKAVL ATQFQDFNLG ERNDAFAPFL
GRGIFTEDGP EWERSRALIR PSLSKAQVAE LPIIEQHVQN LLSRIPGDGS TVDLQQLFFN
FTLDSATHSL LGQPVGFQLS PAGSEAERFS RAFDDAQAFL QVRAKLGPFR GLVRNKAFEV
NCQLVHSAVD RYVSEALGRS ARPRSEDGKP GSMRYDLLSE LASTMTDRTQ IRNELLNVLL
AARDTTASLL SSVFFMLARH PRVWSRLQQE VVQLEGQRPT YDKLREMRYV RAVLNEALRL
FPPVPTNIRC ATCHTSLPRG GGVDGLQPVF VANGTIVHYS IWTMHRSTAI YGSDAEEYRP
ERWLQESDEA PLRPGWGFLP FSGGPRICLG QQKALTEAAY VVIRMLQTFA TVQSRDQRPW
REHMGLVLSS FHGVQVALRH VEG
