Microcin C51 Plasmid Genes: Possible Source of Horizontal Gene Transfer

Fomenko, Dmitri E.; Metlitskaya, Anastasia; Péduzzi, J.; Goulard, Christophe; Катруха, Г. С.; Генинг, Л. В.; Rebuffat, Sylvie; Khmel, I. A.

doi:10.1128/aac.47.9.2868-2874.2003

Cited by 36 publications

(55 citation statements)

References 29 publications

(34 reference statements)

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“…It has also been reported that the peptide MRTGNAD, corresponding to the peptide (12). We synthesized the MRTGNAD peptide as well as the MRTG-NAN peptide encoded by mccA, the structural gene for McC (18,19), and confirmed the previous result (12) that such peptides have no effect on the growth of McC-sensitive cells (data not shown). The addition of these McC peptides (10 M) had no significant effect on the coupled in vitro transcription-translation system (Fig.…”

Section: Has No Effect On In Vitrosupporting

confidence: 68%

“…The phosphoramidate group of the nucleotide part of McC is additionally modified by a propylamine group. Additionally, in mature McC, the peptide moiety, which is encoded by the mccA gene, is modified and the C-terminal asparagine residue specified by mccA is converted to an aspartate (18,19), through an unknown mechanism. In vivo, McC appears to target translation (12).…”

mentioning

confidence: 99%

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Aspartyl-tRNA Synthetase Is the Target of Peptide Nucleotide Antibiotic Microcin C

Metlitskaya

Kazakov

Kommer

et al. 2006

Journal of Biological Chemistry

141

157

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Microcin C is a ribosome-synthesized heptapeptide that contains a modified adenosine monophosphate covalently attached to the C-terminal aspartate. Microcin C is a potent inhibitor of bacterial cell growth. Based on the in vivo kinetics of inhibition of macromolecular synthesis, Microcin C targets translation, through a mechanism that remained undefined. Here, we show that Microcin C is a subject of specific degradation inside the sensitive cell. The product of degradation, a modified aspartyl-adenylate containing an N-acylphosphoramidate linkage, strongly inhibits translation by blocking the function of aspartyl-tRNA synthetase.Microcins are a class of small (Ͻ10 kDa) ribosomally synthesized peptide antibiotics produced by Enterobacteriaceae (1). Whereas some microcins are active as unmodified peptides (2), others are produced as polypeptide precursors that are heavily modified by dedicated maturation enzymes (3). Interest is attached to such post-translationally modified microcins due to their highly unusual structures and the fact that they target important cellular processes that are attractive targets for antibacterial drug development.Genes responsible for microcin production are usually plasmidborne. Plasmids encoding microcin structural and maturation genes also encode determinants of immunity specific to the microcin produced. Based on cross-immunity, post-translationally modified microcins can be subdivided into the B, C, and J types. Microcin B (MccB) 4 is a 43-residue peptide with 8 thiazole and oxazole rings that are synthesized by the McbBCD maturation enzyme complex from multiple serine and cysteine residues present in the MccB precursor (4). MccB is a potent inhibitor of DNA gyrase; it traps the enzyme at the stage of DNA strand passage (5). Microcin J, a 21-amino acid peptide, contains an unusual lactam bond between its N-terminal glycine and the ␦-carboxyl group of an internal glutamate; it assumes a highly unusual threaded-lasso structure (6 -8). MccJ inhibits bacterial RNA polymerase by occluding a narrow channel that is used to traffic transcription substrates, NTPs, to the catalytic center of the enzyme (9, 10).The structure of the subject of this study, Microcin C (McC) is shown in Fig. 1A. McC is a heptapeptide containing a modified adenosine monophosphate covalently attached to its C terminus through an N-acylphosphoramidate linkage (11, 12). The phosphoramidate group of the nucleotide part of McC is additionally modified by a propylamine group. Additionally, in mature McC, the peptide moiety, which is encoded by the mccA gene, is modified and the C-terminal asparagine residue specified by mccA is converted to an aspartate (18, 19), through an unknown mechanism. In vivo, McC appears to target translation (12). Guijarro et al. (12) also reported that large concentrations of McC, as well as of synthetic peptide of the same sequence but without the nucleotide modification, mildly inhibit translation in vitro. They therefore concluded that the peptide part of McC is responsible for transl...

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Section: Has No Effect On In Vitrosupporting

confidence: 68%

mentioning

confidence: 99%

Aspartyl-tRNA Synthetase Is the Target of Peptide Nucleotide Antibiotic Microcin C

Metlitskaya

Kazakov

Kommer

et al. 2006

Journal of Biological Chemistry

141

157

View full text Add to dashboard Cite

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“…Thus, the patellamide cluster was found in a producing strain but was not present in a nonproducer. Because these two strains seem to be very similar by sequencing of several gene classes (chlorophyll a oxidase, 16S rDNA, and the prn NRPS operon), it is possible that pat and similar clusters in Prochloron originate through horizontal gene transfer, as has been proposed for other lantibiotic pathways (35). In fact, the cao and 16S rDNA genes are identical between Prochloron strains, whereas prn is Ͼ98% identical.…”

Section: Correlation Of the Presence Of The Pat Gene Cluster With Patmentioning

confidence: 92%

Patellamide A and C biosynthesis by a microcin-like pathway inProchloron didemni, the cyanobacterial symbiont ofLissoclinum patella

Schmidt

Nelson

Rasko

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

548

717

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Prochloron spp. are obligate cyanobacterial symbionts of many didemnid family ascidians. It has been proposed that the cyclic peptides of the patellamide class found in didemnid extracts are synthesized by Prochloron spp., but studies in which host and symbiont cells are separated and chemically analyzed to identify the biosynthetic source have yielded inconclusive results. As part of the Prochloron didemni sequencing project, we identified patellamide biosynthetic genes and confirmed their function by heterologous expression of the whole pathway in Escherichia coli. The primary sequence of patellamides A and C is encoded on a single ORF that resembles a precursor peptide. We propose that this prepatellamide is heterocyclized to form thiazole and oxazoline rings, and the peptide is cleaved to yield the two cyclic patellamides, A and C. This work represents the full sequencing and functional expression of a marine natural-product pathway from an obligate symbiont. In addition, a related cluster was identified in Trichodesmium erythraeum IMS101, an important bloom-forming cyanobacterium.heterocycle ͉ tunicate ͉ ascidian ͉ genome sequencing ͉ lantibiotic

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“…Table 3 shows that members of the TetR family were detected in 144 microbial genomes belonging to 80 genera and 113 species of gram-positive and ␣-, ␤-, and ␥-proteobacteria, cyanobacteria, and archaea, indicating wide taxonomic distribution. We have found that proteins of the TetR family are encoded both in chromosomes and in plasmids, and the mobility of the latter elements could be a source of the spread of genes in this family via horizontal transfer (147, 383), as is also the case with catabolic genes (77,160,236,410,426), antimicrobial resistance determinants (20,100,124), and 16S rRNA genes (347).…”

Section: Identification Of Tetr Family Members In Dna and Protein Datmentioning

confidence: 99%

The TetR Family of Transcriptional Repressors

Ramos

Martínez-Bueno

Molina‐Henares

et al. 2005

Microbiol Mol Biol Rev

974

1,133

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We have developed a general profile for the proteins of the TetR family of repressors. The stretch that best defines the profile of this family is made up of 47 amino acid residues that correspond to the helix-turn-helix DNA binding motif and adjacent regions in the three-dimensional structures of TetR, QacR, CprB, and EthR, four family members for which the function and three-dimensional structure are known. We have detected a set of 2,353 nonredundant proteins belonging to this family by screening genome and protein databases with the TetR profile. Proteins of the TetR family have been found in 115 genera of gram-positive, α-, β-, and γ-proteobacteria, cyanobacteria, and archaea. The set of genes they regulate is known for 85 out of the 2,353 members of the family. These proteins are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity. The regulatory network in which the family member is involved can be simple, as in TetR (i.e., TetR bound to the target operator represses tetA transcription and is released in the presence of tetracycline), or more complex, involving a series of regulatory cascades in which either the expression of the TetR family member is modulated by another regulator or the TetR family member triggers a cell response to react to environmental insults. Based on what has been learned from the cocrystals of TetR and QacR with their target operators and from their three-dimensional structures in the absence and in the presence of ligands, and based on multialignment analyses of the conserved stretch of 47 amino acids in the 2,353 TetR family members, two groups of residues have been identified. One group includes highly conserved positions involved in the proper orientation of the helix-turn-helix motif and hence seems to play a structural role. The other set of less conserved residues are involved in establishing contacts with the phosphate backbone and target bases in the operator. Information related to the TetR family of regulators has been updated in a database that can be accessed at www.bactregulators.org

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Microcin C51 Plasmid Genes: Possible Source of Horizontal Gene Transfer

Cited by 36 publications

References 29 publications

Aspartyl-tRNA Synthetase Is the Target of Peptide Nucleotide Antibiotic Microcin C

Aspartyl-tRNA Synthetase Is the Target of Peptide Nucleotide Antibiotic Microcin C

Patellamide A and C biosynthesis by a microcin-like pathway inProchloron didemni, the cyanobacterial symbiont ofLissoclinum patella

The TetR Family of Transcriptional Repressors

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