VRTF_PENAE
ID VRTF_PENAE Reviewed; 238 AA.
AC D7PHZ7;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 23.
DE RecName: Full=N-methyltransferase vrtF {ECO:0000303|PubMed:20534346};
DE EC=2.1.1.- {ECO:0000305|PubMed:20534346};
DE AltName: Full=Viridicatumtoxin synthesis protein F {ECO:0000303|PubMed:20534346};
GN Name=vrtF {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: N-methyltransferase; part of the gene cluster that mediates
CC the biosynthesis of viridicatumtoxin, a tetracycline-like fungal
CC 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 -!- 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 methyltransferase superfamily.
CC {ECO:0000255}.
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DR EMBL; GU574477; ADI24931.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PHZ7; -.
DR SMR; D7PHZ7; -.
DR BioCyc; MetaCyc:MON-19277; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR013216; Methyltransf_11.
DR InterPro; IPR016584; MeTrfase_VrtF.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF08241; Methyltransf_11; 1.
DR PIRSF; PIRSF011491; Mtase_YbcY_prd; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Transferase.
FT CHAIN 1..238
FT /note="N-methyltransferase vrtF"
FT /id="PRO_0000436824"
SQ SEQUENCE 238 AA; 26549 MW; A7CD89102B367D97 CRC64;
MTTTTTTDDT QKLDPSASDE VIYKSWDLLI YEIWVLGIVS TWAWGCSTTE YLLPQFRANV
GTNHLDVGSG TGYYLRKGGI PASTRLTLLD LERPALDLGL QRCGRSDARG LQADILQPLP
VIDKFDSVSM YYLLHCIPAS VEDKCAIFKH IKHNMTPDGV IHGANVLGKG VRNDGHFAAY
VRRGVLKAGI FHNLDDNAYD FEHALRMNFE EVETRVVGSV FIFRASRPKL DEGDLLET