Mass spectral database-based methodologies for the annotation and discovery of natural products

Natural products (NPs) have long held a significant position in various fields such as medicine, food, agriculture, and materials. The chemical space covered by NPs is immense but widely unrecognized. Therefore, high-throughput and efficient methodologies for the annotation and discovery of NPs are desired to address the complexity and diversity of NPs-based systems. Mass spectrometry has been demonstrated as a powerful platform for the annotation and discovery of NPs. Mass spectral databases provide vital support for the structural characterization of NPs by integrating extensive mass spectral data and sample information. Meanwhile, the released annotation methodologies are based on a variety of informatics tools, which continuously improve the ability to annotate the structure and properties of compounds. Herein, we review the current mainstream databases and annotation methodologies, with a focus on their advantages and limitations. Prospects for future technological advancements are then discussed in terms of novel applications and research objectives. Through the systematic overview, this review aims to provide valuable insights and reference for mass spectrometry-based NPs annotation, thereby promoting the discovery of novel natural entities.