VRTG_PENAE
ID VRTG_PENAE Reviewed; 307 AA.
AC D7PHZ8;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Lactamase-like protein vrtG {ECO:0000303|PubMed:20534346};
DE EC=3.1.-.- {ECO:0000305|PubMed:20534346};
DE AltName: Full=Viridicatumtoxin synthesis protein G {ECO:0000303|PubMed:20534346};
GN Name=vrtG {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.
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: Lactamase-like protein; 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=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q988B9};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q988B9};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:20534346}.
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 metallo-beta-lactamase superfamily.
CC {ECO:0000305}.
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DR EMBL; GU574477; ADI24932.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PHZ8; -.
DR SMR; D7PHZ8; -.
DR BioCyc; MetaCyc:MON-19276; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF00753; Lactamase_B; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Metal-binding; Zinc.
FT CHAIN 1..307
FT /note="Lactamase-like protein vrtG"
FT /id="PRO_0000436823"
FT ACT_SITE 101
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 101
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 102
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
SQ SEQUENCE 307 AA; 34093 MW; AC0D138DA31EA3B8 CRC64;
MATRIPFDES YWEEYLSGQE ASLPALPAVT QLSPRVTRLL AGNPGIMQLQ GTNTYLVGTG
PARILIDTGE GRPVWHATLA EHLRTHHLTL EYILLTHWHG DHTGGIPDLI AHDPTLQSRI
YKHHPDRGQR PIRDGQRFTV TGATVRAVFT PGHAIDHMCF LIEEEKALLT GDNVLGHGFA
IVQDLAEYMA SLARMAALGC ERGYPAHGAV IENLPAKMQL YIHHNEVRVQ QVITALASVV
KLPGKRVGMT VPEIGRAIYG EVPREIVENA IVPFLSQVLW KLAEDRKVGF EPGEANKRRW
FGLVTQQ
