The need to innovate sample collection and library generation in microbial drug discovery: a focus on academia.

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.

可培养微生物是否仍将是新药先导物的可行来源这一问题，与从环境中采集样本所采用的策略、从这些样本中培养微生物的方法以及创建微生物库的过程息息相关。一个拥有最新的创新色谱和光谱技术、高通量能力以及生物测定法的学术性微生物天然产物（NP）药物研发项目，仍将受其微生物来源库质量的制约。本观点将讨论样本采集和微生物菌株库生成实践的局限性。此外，它将为这些领域的创新提供建议，特别是通过对几种研究不足的细菌门进行靶向培养，以及无靶向地利用质谱法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，并使其前端更具信息性、更高效且更少依赖偶然性。本观点无意对相关文献进行全面综述，且重点关注细菌。从微生物库中发现天然产物的策略，包括各种基因组学和“一株菌多种化合物”（OSMAC）式方法，被视为在样本采集和库创建之后的步骤，因此不在本观点的讨论范围内。