ID   BUAD_ASPBU              Reviewed;         539 AA.
AC   A0A411KZY9;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   08-MAY-2019, sequence version 1.
DT   03-AUG-2022, entry version 9.
DE   RecName: Full=Cytochrome P450 monooxygenase buaD {ECO:0000303|PubMed:30735051};
DE            EC=1.-.-.- {ECO:0000269|PubMed:30735051};
DE   AltName: Full=Burnettramic acids biosynthesis cluster protein D {ECO:0000303|PubMed:30735051};
DE   Flags: Precursor;
GN   Name=buaD {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; QBE85643.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A411KZY9; -.
DR   SMR; A0A411KZY9; -.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular 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; IPR002403; Cyt_P450_E_grp-IV.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00465; EP450IV.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; SSF48264; 1.
PE   3: Inferred from homology;
KW   Antibiotic biosynthesis; Glycoprotein; Heme; Iron; Metal-binding;
KW   Monooxygenase; Oxidoreductase; Signal.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000255"
FT   CHAIN           17..539
FT                   /note="Cytochrome P450 monooxygenase buaD"
FT                   /id="PRO_0000448732"
FT   BINDING         478
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        120
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   CARBOHYD        520
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ   SEQUENCE   539 AA;  60943 MW;  42F30B518D20ACB0 CRC64;
     MLVPVLTLLG TLTATGTLVY HFDERLPVVR FRLLTTFLVL SSGQLLLYAL WKVFLKPLCF
     SPFKHLPKPP LDQWPLWRDH EDGQRGGRAQ VGIIHCRGIL NGERLIVSSP TALAKIASDN
     YTFIKPMAIK LLAGRVLGMG LVLTERDEHK QQRKLFLPPF APKHIRDLYP TFWRKSREVT
     ERMGDEIHAT GAGNGVFEIG EWAARVALDI ITLSTMGKDF GSVRDADAPL AKVYHTVLQP
     TLGHVVIAVL KNFLPARLVE ALPLRSNRHQ GDAYDTIRGV CRDLLREKKD QLAGHHLGGK
     DILSVCLRYE DIAGVDEEEV INQMTTILGA GHETISVGIT WAIYMLCLHR DWQARLREEV
     RATLPSPDRA QESASSADVE RMPLMRAFLE EVLRWYPPIP MTMREPLVDT ELDGQYVPRG
     TRIVVPIKAI NREERYWGPD AKRFSPSRWL KNDREFNPSG GVSSKYGYLS FMHGPRSCVA
     SEFARAEMAC VVSAWVGRFD LDLSDEHFRD EENMRTSNGN FSGKPLEGLY VRAQVLEGW