Mapping Natural Product Biosynthetic Hotspots: Prioritizing Conservation for Medicinal Resources

Abstract

The conservation of biodiversity is important for a number of reasons, one of which being drug discovery. Such conservation would benefit from better understanding of the geographical and genetic patterns of natural product (NP) biosynthesis in plants. Here, we integrate publicly accessible next-generation sequencing and species distribution data of 1,612 woody plant species and their 166 enzymes and establish critical metrics to highlight specific enzyme-rich regions. Our results show that species with patulone-forming prenyltransferase, which catalyzes patulone, a potential bioactive compounds in treating disease mediated by platelet-activating factor, are mainly distributed in the South Central region of the United States, while those with enzymes associated with shikonin derivatives biosynthesis, which are associated with potent anti-cancer activity, are mainly found in certain regions of Asia. Those species distribution patterns are different from the species richness. Moreover, we analyse the complex interplay between numerous enzymes in biosynthetic pathways using shikonin and benzylisoquinoline alkaloids biosynthesis as examples. We detect contrasting geographical distribution patterns, with shikonin derivatives biosynthesis confined to specific regions and benzylisoquinoline alkaloids biosynthesis more globally distributed. These findings suggest policymakers adopt biodiversity conservation policies based on not only the species richness and threat level but also the genetic resources embedded in species. The maps presented in this study will help understand and set such policies.

Phylochemical mapping of natural products onto the plant tree of life using text mining and large language models.

“…For example, a recent study applied a similar idea to identify a link between certain geographic patterns and enzyme biochemical traits. 17 Also, since metabolites are synthesized through enzymes encoded in genome of each individual, the phylogenetic distribution of certain chemicals with genomic and biochemical information could help identify the genetic basis of chemical synthesis. Finally, the comparison of chemical distributions and ecological and geographic patterns could infer potential biological functions and ecological roles of plant specialized metabolites.…”

“…14–16 These analyses have focused on either a broad range of species with a targeted set of metabolites, or a broad range of metabolites across a specific group of species. Such targeted analyses have, for example, helped predict chemical diversity hotspots, 17 helped us understand some of the genetic and evolutionary basis for specialized metabolism, 18,19 and uncovered variant metabolisms with industrial or agricultural applications. 20 These outcomes alone are exciting but also hint at potentially transformative outcomes that could result from broader analyses of plant chemical distributions across the tree of life, i.e., by incorporating wide ranges of both metabolites and species.…”