The Molecules Gateway: A Homogeneous, Searchable Database of 150k Annotated Molecules from Actinomycetes

Natural
products are a sustainable resource for drug discovery,
but their identification in complex mixtures remains a daunting task.
We present an automated pipeline that compares, harmonizes and ranks
the annotations of LC-HRMS data by different tools. When applied to
7,400 extracts derived from 6,566 strains belonging to 86 actinomycete
genera, it yielded 150,000 molecules after processing over 50 million
MS features. The web-based Molecules Gateway provides a highly interactive
access to experimental and calculated data for these molecules, along
with the metadata related to extracts and producer strains. We show
how the Molecules Gateway can be used to rapidly identify known hard
to find microbial products, unreported analogs of known families and
not yet described metabolites. The Molecules Gateway, which complements
available repositories, contains annotated MS data, both acquired
and computationally processed under an identical workflow, making
it suitable for global analyses which reveal a large and untapped
chemical diversity afforded by actinomycetes.

天然产物是药物发现的可持续资源，但在复杂混合物中对其进行鉴定仍是一项艰巨任务。本研究提出一种自动化分析流程，可对不同工具生成的液相色谱-高分辨质谱（LC-HRMS）数据注释结果进行比对、统一化处理与排序。将该流程应用于源自86个放线菌（actinomycete）属的6566株菌株所制备的7400份提取物时，在处理超5000万个质谱（MS）特征后，共得到15万个分子。该基于网页的分子门户（Molecules Gateway）可为这些分子的实验数据与计算预测数据，以及提取物、产毒株相关的元数据，提供高度交互式的访问渠道。本研究展示了如何利用该分子门户快速识别已知的难发现微生物产物、已知家族的未报道类似物以及尚未被表征的代谢物。该分子门户可作为现有资源库的补充，其中包含经统一工作流获取并计算处理后的带注释质谱数据，适用于开展全局分析，以揭示放线菌所蕴含的大量未被开发的化学多样性。