Displaying all 2 publications

Abstract:
Sort:
  1. Snapper: high-sensitive detection of methylation motifs based on Oxford Nanopore reads
    Konanov DN, Babenko VV, Belova AM, Madan AG, Boldyreva DI, Glushenko OE, et al.
    Bioinformatics, 2023 Nov 20.
    PMID: 37982752 DOI: 10.1093/bioinformatics/btad702
    MOTIVATION: The Oxford Nanopore technology has a great potential for the analysis of methylated motifs in genomes, including whole genome methylome profiling. However, we found that there are no methylation motifs detection algorithms which would be sensitive enough and return deterministic results. Thus, the MEME suit does not extract all H. pylori methylation sites de novo even using the iterative manually controlled approach implemented in the most up-to-date methylation analysis tool Nanodisco.

    RESULTS: We present Snapper, a new highly-sensitive approach to extract methylation motif sequences based on a greedy motif selection algorithm. Snapper does not require manual control during the enrichment process and has enrichment sensitivity higher than MEME coupled with Tombo or Nanodisco instruments that was demonstrated on H. pylori strain J99 studied earlier by the PacBio technology and on four external datasets representing different bacterial species. We used Snapper to characterize the total methylome of a new H.pylori strain A45. At least four methylation sites that have not been described for H. pylori earlier were revealed. We experimentally confirmed the presence of a new CCAG-specific methyltransferase and inferred a gene encoding a new CCAAK-specific methyltransferase.

    AVAILABILITY: Snapper is implemented using Python and freely available as a pip package named 'snapper-ont'. Also, Snapper and the demo dataset are available in Zenodo (10.5281/zenodo.10117651).

    SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  2. Fulltext Mining Translation Inhibitors by a Unique Peptidyl-Aminonucleoside Synthetase Reveals Cystocin Biosynthesis and Self-Resistance
    Alferova VA, Zotova PA, Baranova AA, Guglya EB, Belozerova OA, Pipiya SO, et al.
    Int J Mol Sci, 2024 Nov 30;25(23).
    PMID: 39684615 DOI: 10.3390/ijms252312901
    Puromycin (Puro) is a natural aminonucleoside antibiotic that inhibits protein synthesis by its incorporation into elongating peptide chains. The unique mechanism of Puro finds diverse applications in molecular biology, including the selection of genetically engineered cell lines, in situ protein synthesis monitoring, and studying ribosome functions. However, the key step of Puro biosynthesis remains enigmatic. In this work, pur6-guided genome mining is carried out to explore the natural diversity of Puro-like antibiotics. The diversity of biosynthetic gene cluster (BGC) architectures suggests the existence of distinct structural analogs of puromycin encoded by pur-like clusters. Moreover, the presence of tRNACys in some BGCs, i.e., cst-like clusters, leads us to the hypothesis that Pur6 utilizes aminoacylated tRNA as an activated peptidyl precursor, resulting in cysteine-based analogs. Detailed metabolomic analysis of Streptomyces sp. VKM Ac-502 containing cst-like BGC revealed the production of a cysteinyl-based analog of Puro-cystocin (Cst). Similar to puromycin, cystocin inhibits both prokaryotic and eukaryotic translation by the same mechanism. Aminonucleoside N-acetyltransferase CstC inactivated Cst, mediating antibiotic resistance in genetically modified bacteria and human cells. The substrate specificity of CstC originated from the steric hindrance of its active site. We believe that novel aminonucleosides and their inactivating enzymes can be developed through the directed evolution of the discovered biosynthetic machinery.
Related Terms
    Try searching for something
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links