Secondary Metabolites: Green Isolation, AI-Assisted Elucidation, and Mechanistic Insight

Dear Colleagues,

Secondary metabolite research has evolved far beyond the classical “extract–fractionate–test” paradigm, catalyzed by disruptive technologies in analytical chemistry, multi-omics, and artificial intelligence. While earlier Molecules collections have showcased improved extraction protocols and standard bioassays or surveyed specific taxonomic groups, the present Special Issue aims at capturing the next leap: integrative, data-driven discovery and mechanistic insight across all biological kingdoms.

We invite contributions that move beyond the classical workflow and highlight integrative, mechanism-oriented strategies in secondary-metabolite discovery. Submissions should emphasize at least one of the following: (i) innovative isolation/enrichment (green, flow, microfluidic, or otherwise enabling difficult analytes); (ii) advanced structure elucidation (high-resolution MS, cutting-edge NMR including hyphenated or DNP approaches, robust quantum/AI-assisted dereplication and annotation); (iii) omics-enabled discovery (uncovering cryptic pathways or chimeric metabolites); (iv) mechanism-centric bioactivity (target deconvolution, chemoproteomics, phenotypic-to-target workflows, or organ-on-chip); and/or (v) translation and scalability (biotransformations, semisynthesis, or platform technologies that bridge discovery to application).

To promote rigor and reuse, we particularly welcome studies that implement FAIR data practices and deposit raw/curated spectral resources to public repositories. Application domains may include human health, agro-biocontrol, nutraceuticals, flavor and fragrance, and materials, provided the structure–function–mechanism connection is demonstrated.

Scope and novelty criteria (what is wanted/accepted):

• Methodological innovation that clearly exceeds routine practice.
• Integrated chemical + (meta)metabolomic or AI pipelines.
• Convincing mechanistic or target-level insight into bioactivity.
• Demonstrated paths to scalability/translation (flow, biocatalysis, etc.).
• Open, reusable datasets and transparent workflows.
• Out of scope: routine extraction/characterization paired with single bioassays without methodological novelty, integrative analysis, or mechanism.

Formats include original articles, short communications describing breakthrough methodology, and critical reviews that map future directions, e.g., ethical AI in natural-product discovery, FAIR data standards, or the convergence of metabolite annotation with big-data spectral repositories.

By assembling interdisciplinary perspectives, this Special Issue intends to serve as a blueprint for “secondary metabolite science 4.0”, charting a path from nano-scale detection to macro-scale impact. We look forward to your cutting-edge contributions that will redefine the chemical space and biological relevance of secondary metabolites.

Prof. Dr. Niko Radulović
Guest Editors

Dr. Miljana Đorđević Zlatković
Guest Editor Assistant

Manuscript Submission Information

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