Development of “CNPs-MFSA,” a Structural Analysis Support Program to Accelerate the Identification of Natural Compounds Using Mass Spectrometry Data

— Toward Rapid Structural Analysis of Natural Compounds with Complex Structures—

A research group headed by Professor Dr. Wei Li, in collaboration with Dr. Mi Zhang, and Dr. Kouharu Otsuki from the Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Toho University, has devised a new analytical strategy, Modular Fragmentation-based Structural Assembly (MFSA), to identify complex natural compounds from mass spectrometry data. Building on this, the team developed CNPs-MFSA, a computational tool that enables the rapid and highly accurate elucidation of chemical structures. This program can be widely applied in exploring functional natural compounds and natural product drug discovery.
The findings will be published in the academic journal Science Advances on August 15, 2025.

From left: Dr. Zhang Mi, Dr. Kouharu Otsuki, Dr. Wei Li, Dr. Takashi Kikuchi

Key Points of the Announcement

Researchers have proposed a new structural analysis strategy using fragment information from mass spectrometry of complex natural compounds. They developed the structural analysis support program, CNPs-MFSA, based on this strategy.
Applying CNPs-MFSA to daphnane-type diterpenoids from plants in the Thymelaeaceae family enabled reliable structural prediction of 204 compounds, including 105 previously unreported compounds, from extracts from 56 plant species.
Beyond daphnane-type diterpenoids, this strategy applies to other natural compound groups, such as aconitine-type alkaloids, taxane-type diterpenoids, and limonoid-type triterpenes. This can accelerate the discovery of novel bioactive substances derived from natural sources.

Figure. MFSA strategy for specific CNP target annotation. (i) Disassembling the target CNP structure into modules. (ii) Building a pseudo-CNP library. (iii) Recognizing the target CNP using the pseudo-CNP library. (iv) Annotating the module structures of the CNP. (v) Reassembling the annotated modules.

Journal:
Science Advances (August 15, 2025)

Title:
Automated Annotation of Complex Natural Products Using A Modular Fragmentation-based Structure Assembly (MFSA) Strategy

Authors:
Mi Zhang, Kouharu Otsuki, Lingjian Tan, Takashi Kikuchi, Ning Li, Wei Li

DOI:
10.1126/sciadv.adw4693

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