VRTE_PENAE
ID VRTE_PENAE Reviewed; 520 AA.
AC D7PHZ6;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=Cytochrome P450 monooxygenase vrtE {ECO:0000303|PubMed:20534346};
DE EC=1.-.-.- {ECO:0000305|PubMed:20534346};
DE AltName: Full=Viridicatumtoxin synthesis protein E {ECO:0000303|PubMed:20534346};
GN Name=vrtE {ECO:0000303|PubMed:20534346};
OS Penicillium aethiopicum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=36650;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=IBT 5753;
RX PubMed=20534346; DOI=10.1016/j.chembiol.2010.03.015;
RA Chooi Y.H., Cacho R., Tang Y.;
RT "Identification of the viridicatumtoxin and griseofulvin gene clusters from
RT Penicillium aethiopicum.";
RL Chem. Biol. 17:483-494(2010).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=19168978; DOI=10.1038/ja.2008.84;
RA Zheng C.J., Yu H.E., Kim E.H., Kim W.G.;
RT "Viridicatumtoxin B, a new anti-MRSA agent from Penicillium sp. FR11.";
RL J. Antibiot. 61:633-637(2008).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24161266; DOI=10.1021/ja408966t;
RA Chooi Y.H., Hong Y.J., Cacho R.A., Tantillo D.J., Tang Y.;
RT "A cytochrome P450 serves as an unexpected terpene cyclase during fungal
RT meroterpenoid biosynthesis.";
RL J. Am. Chem. Soc. 135:16805-16808(2013).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=27049441; DOI=10.1038/ja.2016.35;
RA Inokoshi J., Nakamura Y., Komada S., Komatsu K., Umeyama H., Tomoda H.;
RT "Inhibition of bacterial undecaprenyl pyrophosphate synthase by small
RT fungal molecules.";
RL J. Antibiot. 69:798-805(2016).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of viridicatumtoxin, a tetracycline-like
CC fungal meroterpenoid with a unique, fused spirobicyclic ring system
CC (PubMed:20534346). The first step of the pathway is the production of
CC the malonamoyl-CoA starter unit for the polyketide synthase vrtA
CC (PubMed:20534346). The aldolase vrtJ may be involved in the synthesis
CC of the malonamate substrate for malonamoyl-CoA synthetase vrtB
CC (PubMed:20534346). The polyketide synthase vrtA then may utilize the
CC malonamoyl-CoA starter unit, followed by sequential condensation of
CC eight malonyl-CoA units to form the polyketide backbone
CC (PubMed:20534346). The cyclization of the last ring could be mediated
CC by the lactamase-like protein vrtG (PubMed:20534346). The proposed
CC post-PKS tailoring steps are an hydroxylation at C5 catalyzed the
CC cytochrome P450 monooxygenase vrtE, a hydroxylation at C12a catalyzed
CC by VrtH and/or VrtI, and an O-methylation by the O-methyltransferase
CC vrtF (PubMed:20534346, PubMed:24161266). VrtC is then proposed to
CC catalyze the transfer of a geranyl group synthesized by vrtD to the
CC aromatic C ring of the tetracyclic polyketide intermediate of
CC viridicatumtoxin to yield previridicatumtoxin (PubMed:20534346).
CC Finally, the cytochrome P450 monooxygenase vrtK catalyzes the
CC spirocyclization of the geranyl moiety of previridicatumtoxin to afford
CC viridicatumtoxin (PubMed:24161266). {ECO:0000269|PubMed:20534346,
CC ECO:0000269|PubMed:24161266}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:20534346}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of viridicatumtoxin, but
CC accumulates a new naphthacenedione intermediate, the 8-O-desmethyl
CC derivative of anthrotainin (PubMed:24161266).
CC {ECO:0000269|PubMed:24161266}.
CC -!- BIOTECHNOLOGY: Viridicatumtoxin and its derivative, viridicatumtoxin B,
CC exhibit anti-methicillin-resistant Staphylococcus aureus (anti-MRSA)
CC activity (PubMed:19168978). Moreover, viridicatumtoxin and a C2 acetyl
CC analog, spirohexaline, have been demonstrated to inhibit bacterial
CC undecaprenyl diphosphate synthase, a potential new target for
CC antibiotic development (PubMed:27049441). {ECO:0000269|PubMed:19168978,
CC ECO:0000269|PubMed:27049441}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; GU574477; ADI24930.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PHZ6; -.
DR SMR; D7PHZ6; -.
DR BioCyc; MetaCyc:MON-19280; -.
DR UniPathway; UPA00213; -.
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; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..520
FT /note="Cytochrome P450 monooxygenase vrtE"
FT /id="PRO_0000436825"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 459
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 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 520 AA; 59877 MW; EE6BB5331F834C0B CRC64;
MFIAAVTHNW MERLAALSLL HYVLGAIFLL LLFHMLSNFF HPGLVDVPGP FAAKFTDLWR
LFKVWQRRFK EDLPGLHASH RSTLIRIGPR MVSCSDPRAV ELIYGFHTEF SKSDMVKAMA
PIYKGKKQPT MFAAADNKTH ARIRKPVAGA YAMTSIMQRM DELFIRPKRA CDIHNWVQYF
AFDMVLEMTM SRNLGFMKAG GDVDGVLKQL QKDLDYRGIA LAMPIIDRIW RLNPVSKFFK
PKQSGHFAMR CKRILEDRMA YEKSLDSRTQ QQQDQKPHDF AHRFLEAQRK DPSISDGQLI
GYMQANLIAG SDTTAVVMRT AIYYTLKQPW ILQRLVTELD QYHGPLPVPF RIARFEMPFC
GAIVREALRR HFAFIGMMER QTPPCGVVMP DGRRLPGGVV IGMHGDLIGR DRAIFGEDAD
EFNPLRWLAR PGEPEAKYQE RLRAMNAHDL AFGHGPRGCI GKHVAEMEIY KFIPTFFALI
QPRFMRPEQS WTVRQLFVFK QSGMDMMLDW RQGKGLQSMA
