suggest that these genes were likely acquired by the last common ancestor of octocorals, through de novo evolution (e.g., gene duplication) or horizontal gene transfer. Our phylogenetic analysis of TSs from marine invertebrates, microorganisms, and plants not only confirms coral TSs as a monophyletic group but also reveals the evolutionary relationships among marine biflorane, eunicellane, and cembrane synthases. This insight guided the evolution-based engineering of PcTS1, resulting in the production of a variety of products including three compounds with new skeletons (Fig. ). This approach not only underscores the effectiveness of this methodology but also expands the pool of potential biocatalysts for terpene synthesis. Despite the production of numerous new compounds through evolution-guided mutations, the anticipated eunicellane and cembrane skeletons were not achieved. This could be due to the insufficiency of a single amino acid mutation in directing a skeleton transformation.