Stepanyshyn Anastasia, Rückert-Reed Christian, Busche Tobias, Yaruta Bohdan, Andreo-Vidal Andres, Marinelli Flavia, Kalinowski Jörn, Yushchuk Oleksandr
Department of Genetics and Biotechnology, Ivan Franko National University of Lviv, 79005 Lviv, Ukraine.
Technology Platform Genomics, CeBiTec, Bielefeld University, Sequenz 1, 33615 Bielefeld, Germany.
Genes (Basel). 2024 Dec 22;15(12):1651. doi: 10.3390/genes15121651.
Glycopeptide antibiotics (GPAs) are a very successful class of clinically relevant antibacterials, used to treat severe infections caused by Gram-positive pathogens, e.g., multidrug resistant and methicillin-resistant staphylococci. The biosynthesis of GPAs is coded within large biosynthetic gene clusters (BGCs). In recent years, modern DNA sequencing technologies have allowed the identification and characterization of multiple novel GPA BGCs, leading to the discovery of novel compounds. Our previous research anticipated that the genome of DSM 45807 carries a novel GPA BGC, although the genomic sequence quality available at that time did not allow us to characterize its organization properly.
To address this gap, in the current work we aimed to produce a complete genome assembly of DSM 45807, and to identify and analyze the corresponding GPA BGC.
Bioinformatic and microbiological methods were utilized in this research.
We de novo sequenced and completely assembled the genome of DSM 45807, and fully characterized the BGC of interest, named . This BGC has an unusual gene organization and it contains four genes for sulfotransferases, which are considered to be rare in GPA BGCs. Our pathway prediction indicated that encodes the biosynthesis of a putatively novel GPA, although we were not able to detect any GPA production under different cultivation conditions, implying that pathway is inactive.
Our results indicate as a promising source for new GPA tailoring enzymes.
糖肽类抗生素(GPAs)是一类非常成功的具有临床相关性的抗菌药物,用于治疗由革兰氏阳性病原体引起的严重感染,例如耐多药和耐甲氧西林葡萄球菌。GPAs的生物合成由大型生物合成基因簇(BGCs)编码。近年来,现代DNA测序技术使得鉴定和表征多个新型GPA BGCs成为可能,从而发现了新型化合物。我们之前的研究预计DSM 45807的基因组携带一个新型GPA BGC,尽管当时可用的基因组序列质量不允许我们恰当地表征其结构。
为了填补这一空白,在当前工作中,我们旨在生成DSM 45807的完整基因组组装,并鉴定和分析相应的GPA BGC。
本研究采用了生物信息学和微生物学方法。
我们对DSM 45807的基因组进行了从头测序和完全组装,并对感兴趣的BGC进行了全面表征,命名为 。这个BGC具有不寻常的基因结构,并且包含四个磺基转移酶基因,这在GPA BGCs中被认为是罕见的。我们的途径预测表明 编码一种推测的新型GPA的生物合成,尽管我们在不同培养条件下未能检测到任何GPA的产生,这意味着 途径是无活性的。
我们的结果表明 是新型GPA定制酶的一个有前景的来源。