Atomic basis for functional evolution of plant lanosterol synthase

Summary Lanosterol synthase (LAS) and cycloartenol synthase (CAS) use 2,3‐oxidosqualene as their substrate to produce lanosterol and cycloartenol for biosynthesis of essential sterols in animals and fungi (lanosterol) and plants (cycloartenol), respectively. Although LASs are also found in plants, their evolutionary origin and the question of whether their catalytic mechanism aligns with animal/fungal LAS remain unresolved. In this study, we use QM/MM MD simulations to reveal the atomic‐level catalytic mechanisms of LASs from all three lineages. Our simulations reveal a dominant reaction path from a C8 cation intermediate to lanosterol for plant LASs, which is different from the reaction path for animal and fungal LASs. Phylogenetic and microcollinearity analyses demonstrate that plant LASs evolved from an ancestral plant CAS and are restricted to eudicots. Combining these findings with mechanistic insights, we demonstrate that plant LASs have undergone convergent evolution with their animal and fungal counterparts, independently acquiring a role in root development. This study establishes the lanosterol biosynthesis pathway as a remarkable example of convergent evolution across eukaryotes, having arisen independently in plants, animals, and fungi. By defining the role of plant LAS in root development, this research provides key molecular targets for breeding stress‐resilient crops.