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The need to innovate sample collection and library generation in microbial drug discovery: a focus on academia.
Natural Product Reports ( IF 11.9 ) Pub Date : 2020-7-24 , DOI: 10.1039/d0np00029a
Antonio Hernandez 1 , Linh T Nguyen 2 , Radhika Dhakal 1 , Brian T Murphy 1
Affiliation  

The question of whether culturable microorganisms will continue to be a viable source of new drug leads is inherently married to the strategies used to collect samples from the environment, the methods used to cultivate microorganisms from these samples, and the processes used to create microbial libraries. An academic microbial natural products (NP) drug discovery program with the latest innovative chromatographic and spectroscopic technology, high-throughput capacity, and bioassays will remain at the mercy of the quality of its microorganism source library. This viewpoint will discuss limitations of sample collection and microbial strain library generation practices. Additionally, it will offer suggestions to innovate these areas, particularly through the targeted cultivation of several understudied bacterial phyla and the untargeted use of mass spectrometry and bioinformatics to generate diverse microbial libraries. Such innovations have potential to impact downstream therapeutic discovery, and make its front end more informed, efficient, and less reliant on serendipity. This viewpoint is not intended to be a comprehensive review of contributing literature and was written with a focus on bacteria. Strategies to discover NPs from microbial libraries, including a variety of genomics and “OSMAC” style approaches, are considered downstream of sample collection and library creation, and thus are out of the scope of this viewpoint.

中文翻译:

微生物药物发现中创新样品收集和文库生成的需要:学术界的关注。

可培养微生物是否将继续成为新药先导化合物的可行来源,这个问题本质上与从环境中收集样品的策略、从这些样品中培养微生物的方法以及创建微生物库的过程密切相关。具有最新创新色谱和光谱技术、高通量能力和生物测定的学术微生物天然产物 (NP) 药物发现计划将继续受到其微生物源库质量的影响。该观点将讨论样本收集和微生物菌株库生成实践的局限性。此外,它将提供这些领域的创新建议,特别是通过有针对性地培养几个待研究的细菌门,以及无针对性地使用质谱和生物信息学来生成多样化的微生物库。此类创新有可能影响下游的治疗发现,并使其前端更加知情、高效,并且更少依赖偶然性。这一观点并非旨在对贡献文献进行全面回顾,而是以细菌为重点撰写的。从微生物文库中发现纳米粒子的策略,包括各种基因组学和“OSMAC”风格的方法,被认为是样本收集和文库创建的下游,因此不属于该观点的范围。
更新日期:2020-07-24
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