Chemotaxonomic Map of Labdane Diterpenoids in Acanthaceae

Terpenoids are among the most chemically diverse natural product classes in the plant kingdom and are a source of numerous nature-inspired human medicines. One specific subclass, diterpenoids, defined by a C20 skeleton, includes attractive compounds such as the anticancer drug Taxol, the sweetener steviol, and the plant hormone gibberellin. One specialized group of ent-labdane (bicyclic) diterpenoids, primarily reported from the genus Andrographis (Acanthaceae), is the source of andrographolides, a diverse array of bioactive scaffolds with anti-inflammatory, antioxidant, anticancer, antimicrobial, and antihyperglycemic properties. Using high-throughput metabolomics, we set out to examine the molecular diversity within the Acanthaceae family, alongside other taxonomic lineages reported to accumulate diterpenoids. In a combined metabolomic investigation of 31 genera spanning Acanthaceae, Lamiaceae, and Poaceae, we annotated several reported andrographolide-type labdane diterpenoids and characteristic compounds unique to Acanthaceae. Integration of chemical, geographic, and taxonomic metadata with literature-driven assessments helped paint a chemotaxonomic and phylogeographic distribution map of andrographolide-type labdane diterpenoids across 163 countries. We found several species accumulate at least seven andrographolide-type compounds and another 17 labdane diterpenoids in our analysis. We conclude that labdane diterpenoid accumulation is more widespread, with multicontinental and shared evolutionary origins, than previously recognized.