Microbial metabolites play a critical role in regulating ecosystems, including the human body and its microbiota. However, understanding the physiologically relevant role of these molecules, especially through liquid chromatography tandem mass spectrometry (LC-MS/MS)-based untargeted metabolomics, poses significant challenges and often requires manual parsing of a large amount of literature, databases, and webpages. To address this gap, we established the Collaborative Microbial Metabolite Center knowledgebase (CMMC-KB), a platform that fosters collaborative efforts within the scientific community to curate knowledge about microbial metabolites. The CMMC-KB aims to collect comprehensive information about microbial molecules originating from microbial biosynthesis, drug metabolism, exposure-related molecules, food, host-derived molecules, and, whenever available, their known activities. Molecules from other sources, including host-produced, dietary, and pharmaceutical compounds, are also included. By enabling direct integration of this knowledgebase with downstream analytical tools, including molecular networking, we can deepen insights into microbiota and their metabolites, ultimately advancing our understanding of microbial ecosystems.

Building custom data analysis platforms has traditionally required extensive software engineering expertise, limiting access for many researchers. Here, I demonstrate that modern large language models...

Quantification is a challenge for non-targeted analysis (NTA) with liquid chromatography–high resolution mass spectrometry (LC–HRMS), due to the lack of analytical standards. Quantification via struct...

In/postsource fragments (ISFs) arise during electrospray ionization or ion transfer in mass spectrometry when molecular bonds break, generating ions that can complicate data interpretation. Although ISFs have been recognized for decades, their contribution to untargeted metabolomics─particularly in the context of the so-called “dark matter” (unannotated MS or MS/MS spectra) and the “dark metabolome” (unannotated molecules)─remains unsettled. This ongoing debate reflects a central tension: while some caution against overinterpreting unidentified signals lacking biological evidence, others argue that dismissing them too quickly risks overlooking genuine molecular discoveries. These discussions also raise a deeper question: what exactly should be considered part of the metabolome? As metabolomics advances toward large-scale data mining and high-throughput computational analysis, resolving these conceptual and methodological ambiguities has become essential. In this perspective, we propose a refined definition of the “dark metabolome” and present a systematic overview of ISFs and related ion forms, including adducts and multimers. We examine their impact on metabolite annotation, experimental design, statistical analysis, computational workflows, and repository-scale data mining. Finally, we provide practical recommendations─including a set of dos and do nots for researchers and reviewers─and discuss the broader implications of ISFs for how the field explores unknown molecular space. By embracing a more nuanced understanding of ISFs, metabolomics can achieve greater rigor, reduce misinterpretation, and unlock new opportunities for discovery.

Comprehensive metabolomics requires robust and efficient analytical techniques capable of addressing the chemical diversity, complexity, and high sample throughput demands characteristic of large-scal...

An advanced metabolomic workflow featuring expert knowledge-tailored mass spectral queries and multi-informative molecular networking was applied to French DNA-barcoded collections of Amanita species ...

The study examines the impact of salinity on surface properties of freshwater Synechocystis sp. PCC6803, marine Synechococcus sp. PCC8806 and alkaliphilic Spirulina platensis. The differences in memb...

Abstract. Secondary or specialized metabolites show extraordinary structural diversity and potent biological activities relevant for clinical and industria

Driven by eutrophication and global warming, the occurrence and frequency of harmful cyanobacteria blooms (CyanoHABs) are increasing worldwide, posing…

Decade-long field measurements and modelling show that projected ocean temperatures could restrict cell division rates of an important marine cyanobacterium.

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Analytical ChemistryDOI: 10.1021/acs.analchem.5c02591

The exponential growth of untargeted metabolomics data, now reaching billions of mass spectra in public repositories, benefits from reannotation strategies for data reuse. While tandem mass spectromet...

Elucidating reaction mechanisms in heterogeneous catalysis demands real-time tracking of transient species at the solid–liquid interface. To address limitations in directly probing surface processes with conventional mass spectrometry (MS), this work develops an innovative “in-source reaction” strategy by integrating the reactor with the electrospray ionization (ESI) source. Diverse catalysts (e.g., g-C3N4, TiO2, zeolites, and Pd/C) were robustly immobilized within a glass probe (GP), integrating the microreactor and ionization source. This enables direct, subsecond resolution detection of species desorbing from catalytic surfaces. This strategy has been successfully verified by in-situ tracking of the photocatalytic degradation of Brilliant Green (BG) and other dyes. Over 40 intermediates in BG photocatalytic degradation were detected, with different evolution pathways revealing distinct mechanisms for g-C3N4 under visible light and TiO2 under UV light. Besides photocatalyst, typical solid catalysts were also immobilized on the inner wall of the GP to study the initial contact reactions of a β-O-4 model compound of lignin conversion. The obvious dehydrogenation of surface-adsorbed GGGE on Pd surface was observed by in-situ monitoring, while basic or amphoteric support surface spontaneously induced cyclization of GGGE, even without the input of external energy such as light and heat. This method provides a novel, extremely feasible, and sensitive strategy for tracking surface processes in liquid–solid heterogeneous catalytic reactions and holds promise for broader application to diverse catalytic reaction systems in the future.