%0 Journal Article %T Spatial Evidence Changes Biosynthetic Inference: Integrating Mass-Spectrometry Imaging, Spatial Transcriptomics, Cell-Type Identity, and Tissue Anatomy in Medicinal-Plant Pathway Reconstruction %A Luca Ferraro %A Matteo Ricci %A Giulia Moretti %A Paolo Greco %J Specialty Journal of Pharmacognosy, Phytochemistry, and Biotechnology %@ 3062-441X %D 2026 %V 6 %N 1 %R 10.51847/aY0Vz57uGP %P 22-30 %X Reconstructing medicinal-plant biosynthetic pathways increasingly requires more than identifying enzymes, pathway genes, and candidate regulatory relationships. Conventional genomic, transcriptomic, biochemical, and heterologous-reconstruction approaches can establish pathway membership and reaction competence while leaving unresolved where pathway steps occur within intact tissues, whether intermediates move between cell types, and whether metabolite accumulation identifies synthesis, transport, or storage. This article develops a proposed spatial evidence-integration model that treats mass-spectrometry imaging, spatial transcriptomics, dissociative single-cell or single-nucleus profiles, cell-type identity, and tissue anatomy as complementary but non-equivalent evidence. The central argument is that spatial concordance should strengthen, but not close, biosynthetic inference, whereas spatial discordance can be diagnostically useful when competing explanations such as transport, temporal mismatch, turnover, or sequestration remain plausible. The model therefore separates evidence for molecular identity, cellular expression, anatomical position, chemical localization, biological movement, and orthogonal functional validation rather than collapsing them into a single confidence score. Medicinal-plant examples involving monoterpene indole alkaloids, taxoids, ginsenosides, artemisinin-related metabolism, and securinine-associated chemistry illustrate how cell-resolved and spatial evidence can refine pathway hypotheses. The framework remains bounded by analytical resolution, metabolite-identification confidence, cross-modal registration, transcript–metabolite timing differences, transport, tissue heterogeneity, and species-specific anatomy. Its intended role is hypothesis refinement and validation design, not causal proof from spatial co-occurrence alone. %U https://galaxypub.co/article/spatial-evidence-changes-biosynthetic-inference-integrating-mass-spectrometry-imaging-spatial-tran-6anljtxylwj6mh8