Le Loarer Alexandre, Marcellin-Gros Rémy, Dufossé Laurent, Bignon Jérôme, Frédérich Michel, Ledoux Allison, Queiroz Emerson Ferreira, Wolfender Jean-Luc, Gauvin-Bialecki Anne, Fouillaud Mireille
Laboratory of Chemistry and Biotechnology of Natural Products, Faculty of Science and Technology, University of La Réunion, 15 Avenue René Cassin, CS 92003, CEDEX 09, 97744 Saint-Denis, France.
Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU-Rue Michel-Servet 1, CH-1211 Geneva, Switzerland.
Microorganisms. 2023 Mar 8;11(3):697. doi: 10.3390/microorganisms11030697.
Despite considerable advances in medicine and technology, humanity still faces many deadly diseases such as cancer and malaria. In order to find appropriate treatments, the discovery of new bioactive substances is essential. Therefore, research is now turning to less frequently explored habitats with exceptional biodiversity such as the marine environment. Many studies have demonstrated the therapeutic potential of bioactive compounds from marine macro- and microorganisms. In this study, nine microbial strains isolated from an Indian Ocean sponge, were screened for their chemical potential. The isolates belong to different phyla, some of which are already known for their production of secondary metabolites, such as the actinobacteria. This article aims at describing the selection method used to identify the most promising microorganisms in the field of active metabolites production. The method is based on the combination of their biological and chemical screening, coupled with the use of bioinformatic tools. The dereplication of microbial extracts and the creation of a molecular network revealed the presence of known bioactive molecules such as staurosporin, erythromycin and chaetoglobosins. Molecular network exploration indicated the possible presence of novel compounds in clusters of interest. The biological activities targeted in the study were cytotoxicity against the HCT-116 and MDA-MB-231 cell lines and antiplasmodial activity against 3D7. SH-123 and SH-78 strains actually showed remarkable cytotoxic and antiplasmodial activities, while SH-82 demonstrated promising antiplasmodial effects. The ranking of the microorganisms as a result of the different screening steps allowed the selection of a promising strain, SH-82, as a premium candidate for the discovery of new drugs.
尽管医学和技术取得了长足进步,但人类仍面临许多致命疾病,如癌症和疟疾。为了找到合适的治疗方法,发现新的生物活性物质至关重要。因此,目前的研究正转向生物多样性异常丰富但较少被探索的栖息地,如海洋环境。许多研究已经证明了海洋大型生物和微生物中生物活性化合物的治疗潜力。在本研究中,对从印度洋海绵中分离出的9株微生物菌株的化学潜力进行了筛选。这些分离株属于不同的门,其中一些已经因其产生次生代谢产物而闻名,如放线菌。本文旨在描述用于识别活性代谢产物生产领域中最有前景的微生物的选择方法。该方法基于生物筛选和化学筛选的结合,并结合生物信息学工具的使用。微生物提取物的去重复和分子网络的创建揭示了已知生物活性分子的存在,如星形孢菌素、红霉素和毛壳菌素。分子网络探索表明在感兴趣的簇中可能存在新化合物。该研究针对的生物活性是对HCT - 116和MDA - MB - 231细胞系的细胞毒性以及对3D7、SH - 123和SH - 78菌株的抗疟活性。SH - 123和SH - 78菌株实际上表现出显著的细胞毒性和抗疟活性,而SH - 82表现出有前景的抗疟效果。通过不同筛选步骤对微生物进行排名,从而选择了有前景的菌株SH - 82作为发现新药的优质候选菌株。