Structure of a Sulfated Capsular Polysaccharide from the Marine Bacterium Cobetia marina KMM 1449 and a Genomic Insight into Its Biosynthesis.

IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Marine Drugs Pub Date : 2025-01-08 DOI:10.3390/md23010029
Maxim S Kokoulin, Yulia V Savicheva, Alina P Filshtein, Ludmila A Romanenko, Marina P Isaeva
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Abstract

Some marine and extremophilic microorganisms are capable of synthesizing sulfated polysaccharides with a unique structure. A number of studies indicate significant biological properties of individual sulfated polysaccharides, such as antiproliferative activity, which makes them a promising area for further research. In this study, the capsular polysaccharide (CPS) was obtained from the bacterium Cobetia marina KMM 1449, isolated from a marine sediment sample collected along the shore of the Sea of Japan. The CPS was isolated by saline solution, purified by a series of chromatographic procedures, and studied by chemical methods along with 1D and 2D 1H and 13C NMR spectroscopy. The following new structure of the CPS from C. marina KMM 1449 was established and consisted of sulfated and simultaneously phosphorylated disaccharide repeating units: →4)-α-L-Rhap2S-(1→3)-β-D-Manp6PGro-(1→. To elucidate the genetic basis of the CPS biosynthesis, the whole genomic sequence of C. marina KMM 1449 was obtained. The CPS biosynthetic gene cluster (BGC) of about 70 genes composes four regions encoding nucleotide sugar biosynthesis (dTDP-Rha and GDP-Man), assembly (GTs genes), translocation (ABC transporter genes), sulfation (PAPS biosynthesis and sulfotransferase genes) and lipid carrier biosynthesis (wcb operon). Comparative analysis of the CPS BGCs from available Cobetia genomes showed the presence of KMM 1449-like CPS BGC among strains of all three Cobetia species. The study of new natural sulfated polysaccharides, as well as the elucidation of the pathways of their biosynthesis, provides the basis for the development of potential anticancer drugs.

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海洋细菌Cobetia marina KMM 1449硫酸酸化荚膜多糖的结构及其生物合成的基因组学研究。
一些海洋微生物和嗜极微生物能够合成具有独特结构的硫酸酸化多糖。许多研究表明,单个硫酸酸化多糖具有显著的生物学特性,如抗增殖活性,这使其成为一个有希望进一步研究的领域。在本研究中,从日本海沿岸收集的海洋沉积物样品中分离出Cobetia marina KMM 1449细菌,获得荚膜多糖(CPS)。采用生理盐水分离CPS,经一系列色谱纯化,并用1D和2D 1H和13C NMR进行化学方法研究。由硫酸酸化和同时磷酸化的双糖重复单元组成的C. marina KMM 1449 CPS的新结构为:→4)-α- l - rhap2s -(1→3)-β- d - manp6pgro -(1→)。为了阐明CPS生物合成的遗传基础,我们获得了C. marina KMM 1449的全基因组序列。CPS生物合成基因簇(BGC)由大约70个基因组成,包括编码核苷酸糖生物合成(dTDP-Rha和GDP-Man)、组装(GTs基因)、易位(ABC转运蛋白基因)、硫酸化(PAPS生物合成和硫转移酶基因)和脂质载体生物合成(wcb操纵子)四个区域。通过对3个种属的CPS BGC进行比较分析,发现3个种属中均存在KMM 1449样CPS BGC。新型天然硫酸多糖的研究及其生物合成途径的阐明,为潜在抗癌药物的开发提供了基础。
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来源期刊
Marine Drugs
Marine Drugs 医学-医药化学
CiteScore
9.60
自引率
14.80%
发文量
671
审稿时长
1 months
期刊介绍: Marine Drugs (ISSN 1660-3397) publishes reviews, regular research papers and short notes on the research, development and production of drugs from the sea. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible, particularly synthetic procedures and characterization information for bioactive compounds. There is no restriction on the length of the experimental section.
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