AUSG_PENBI
ID AUSG_PENBI Reviewed; 530 AA.
AC A0A0F7TN60;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 1.
DT 03-AUG-2022, entry version 24.
DE RecName: Full=Cytochrome P450 monooxygenase ausG {ECO:0000303|PubMed:29076725};
DE EC=1.-.-.- {ECO:0000305|PubMed:29076725};
DE AltName: Full=Austinoid biosynthesis clusters protein G {ECO:0000303|PubMed:29076725};
GN Name=ausG {ECO:0000303|PubMed:29076725}; ORFNames=PMG11_06809;
OS Penicillium brasilianum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=104259;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MG11;
RX PubMed=26337871; DOI=10.1128/genomea.00724-15;
RA Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Brakhage A.A.,
RA Valiante V.;
RT "Draft genome sequence of the fungus Penicillium brasilianum MG11.";
RL Genome Announc. 3:0-0(2015).
RN [2]
RP FUNCTION.
RX PubMed=27602587; DOI=10.1021/jacs.6b08424;
RA Matsuda Y., Iwabuchi T., Fujimoto T., Awakawa T., Nakashima Y., Mori T.,
RA Zhang H., Hayashi F., Abe I.;
RT "Discovery of key dioxygenases that diverged the paraherquonin and
RT acetoxydehydroaustin pathways in Penicillium brasilianum.";
RL J. Am. Chem. Soc. 138:12671-12677(2016).
RN [3]
RP FUNCTION.
RX PubMed=29076725; DOI=10.1021/acschembio.7b00814;
RA Mattern D.J., Valiante V., Horn F., Petzke L., Brakhage A.A.;
RT "Rewiring of the austinoid biosynthetic pathway in filamentous fungi.";
RL ACS Chem. Biol. 12:2927-2933(2017).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster B
CC that mediates the biosynthesis of the fungal meroterpenoid
CC acetoxydehydroaustin (PubMed:29076725). The first step of the pathway
CC is the synthesis of 3,5-dimethylorsellinic acid by the polyketide
CC synthase ausA (By similarity). 3,5-dimethylorsellinic acid is then
CC prenylated by the polyprenyl transferase ausN (By similarity). Further
CC epoxidation by the FAD-dependent monooxygenase ausM and cyclization by
CC the probable terpene cyclase ausL lead to the formation of
CC protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to
CC spiro-lactone preaustinoid A3 by the combined action of the FAD-binding
CC monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity).
CC Acid-catalyzed keto-rearrangement and ring contraction of the
CC tetraketide portion of preaustinoid A3 by ausJ lead to the formation of
CC preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the
CC help of ausH, is involved in the next step by transforming preaustinoid
CC A4 into isoaustinone which is in turn hydroxylated by the P450
CC monooxygenase ausI to form austinolide (By similarity). The cytochrome
CC P450 monooxygenase ausG then modifies austinolide to austinol (By
CC similarity). Austinol is further acetylated to austin by the O-
CC acetyltransferase ausP, which spontaneously changes to dehydroaustin
CC (PubMed:29076725). The cytochrome P450 monooxygenase then converts
CC dehydroaustin is into 7-dehydrodehydroaustin (PubMed:29076725). The
CC hydroxylation catalyzed by ausR permits the second O-acetyltransferase
CC ausQ to add an additional acetyl group to the molecule, leading to the
CC formation of acetoxydehydroaustin (PubMed:29076725). Due to genetic
CC rearrangements of the clusters and the subsequent loss of some enzymes,
CC the end product of the Penicillium brasilianum austinoid biosynthesis
CC clusters is acetoxydehydroaustin (PubMed:29076725).
CC {ECO:0000250|UniProtKB:Q5AR32, ECO:0000269|PubMed:29076725}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|PubMed:29076725}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- MISCELLANEOUS: In A.calidoustus, the austinoid gene cluster lies on a
CC contiguous DNA region, while clusters from E.nidulans and P.brasilianum
CC are split in their respective genomes. Genetic rearrangements provoked
CC variability among the clusters and E.nidulans produces the least number
CC of austionoid derivatives with the end products austinol and
CC dehydroaustinol, while P.brasilianum can produce until
CC acetoxydehydroaustin, and A.calidoustus produces the highest number of
CC identified derivatives. {ECO:0000305|PubMed:29076725}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; CDHK01000006; CEJ58139.1; -; Genomic_DNA.
DR EnsemblFungi; CEJ58139; CEJ58139; PMG11_06809.
DR OrthoDB; 572303at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000042958; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 3: Inferred from homology;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..530
FT /note="Cytochrome P450 monooxygenase ausG"
FT /id="PRO_0000453838"
FT TRANSMEM 31..51
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 470
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"
SQ SEQUENCE 530 AA; 59058 MW; 8AC245F230F57C43 CRC64;
MAMVTPGLWA NFSHSSHELG IANGFEFLNS LLVAYRLPGL LLLFSITIIL FQPLRKKSDL
PLINSGKGPF SILRGYRSRK TFAAELPRLV AEGLSKASAF RIAAPDGVNI VLAPSYAHEI
GEHPDLNPGP IAGDEFNCHI DGFEVFAQLG TSDVISESVR TRLTRQLTKL TPLLTSETAL
LLQSQWKDAP NWVEVSPHET AMFILSRLSS LVFVGDDLGR NPDWVHILTS YNNEAFAAAE
ELNLWPQILR PLVAHLKPSC RQLRRYIRDA RALLIPVIEQ RHHAQSQGDR REYNDAIEWL
NETSHSLAQS YDPLLSQMLL AIGSFHTSSD LLGQVLLDLC MRQDWEVLVG ELRKEIISSL
QGVGWDKISL NNLKLMDSVL KESQRLKPAS TVTMGRYASR EIILSDGTRI PKGSTVFIAN
VAMRDPNIYP DPDVFIPDRF TTRREKGDSS AYLVSASPEH IGFGLGRHAC PGRFFAANEV
KIVLSHMLLK YDIKLPDNGA AVAPSTSGIF LETNPNARIC VRRRKEEILI