Department of Molecular Evolution and Plant Systematics & Herbarium (LZ), Institute of Biology, Leipzig University, D-04103 Leipzig, Germany.
Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, D-06120 Halle (Saale), Germany.
Proc Natl Acad Sci U S A. 2020 Jun 2;117(22):12444-12451. doi: 10.1073/pnas.1915277117. Epub 2020 May 11.
Antibiotic resistance and viral diseases are rising around the world and are becoming major threats to global health, food security, and development. One measure that has been suggested to mitigate this crisis is the development of new antibiotics. Here, we provide a comprehensive evaluation of the phylogenetic and biogeographic patterns of antiinfective compounds from seed plants in one of the most species-rich regions on Earth and identify clades with naturally occurring substances potentially suitable for the development of new pharmaceutical compounds. Specifically, we combine taxonomic and phylogenetic data for >7,500 seed plant species from the flora of Java with >16,500 secondary metabolites and 6,255 georeferenced occurrence records to 1) identify clades in the phylogeny that are characterized by either an overrepresentation ("hot clades") or an underrepresentation ("cold clades") of antiinfective compounds and 2) assess the spatial patterns of plants with antiinfective compounds relative to total plant diversity across the region. Across the flora of Java, we identify 26 "hot clades" with plant species providing a high probability of finding antibiotic constituents. In addition, 24 "cold clades" constitute lineages with low numbers of reported activities but which have the potential to yield novel compounds. Spatial patterns of plant species and metabolite diversity are strongly correlated across Java, indicating that regions of highest species diversity afford the highest potential to discover novel natural products. Our results indicate that the combination of phylogenetic, spatial, and phytochemical information is a useful tool to guide the selection of taxa for efforts aimed at lead compound discovery.
抗生素耐药性和病毒性疾病在全球范围内不断上升，正在成为全球健康、粮食安全和发展的主要威胁。有人建议采取措施来缓解这场危机，其中包括开发新的抗生素。在这里，我们对地球上物种最丰富的地区之一——爪哇植物区系中的种子植物抗感染化合物的系统发育和生物地理模式进行了全面评估，并确定了具有潜在天然物质的进化枝，这些物质可能适合开发新的药物化合物。具体来说，我们将来自爪哇植物区系的 >7500 种种子植物的分类和系统发育数据与 >16500 种次生代谢物和 6255 个地理参考出现记录相结合，以 1）确定系统发育中以抗感染化合物过度表达（“热点进化枝”）或表达不足（“冷点进化枝”）为特征的进化枝；2）评估具有抗感染化合物的植物相对于该地区总植物多样性的空间分布模式。在爪哇植物区系中，我们确定了 26 个具有高概率发现抗生素成分的植物物种的“热点进化枝”。此外，24 个“冷点进化枝”构成了报道活动数量较少但具有产生新型化合物潜力的进化枝。在整个爪哇，植物物种和代谢物多样性的空间模式高度相关，这表明物种多样性最高的地区最有可能发现新的天然产物。我们的结果表明，系统发育、空间和植物化学信息的结合是指导选择分类群以进行先导化合物发现工作的有用工具。
