Bacterial diterpene synthases: new opportunities for mechanistic enzymology and engineered biosynthesis

Diterpenoid biosynthesis has been extensively studied in plants and fungi, yet cloning and engineering diterpenoid pathways in these organisms remain challenging. Bacteria are emerging as prolific producers of diterpenoid natural products, and bacterial diterpene synthases are poised to make significant contributions to our understanding of terpenoid biosynthesis. Here we will first survey diterpenoid natural products of bacterial origin and briefly review their biosynthesis with emphasis on diterpene synthases (DTSs) that channel geranylgeranyl diphosphate to various diterpenoid scaffolds. We will then highlight differences of DTSs of bacterial and higher organism origins and discuss the challenges in discovering novel bacterial DTSs. We will conclude by discussing new opportunities for DTS mechanistic enzymology and applications of bacterial DTS in biocatalysis and metabolic pathway engineering.

► Cloning and engineering diterpenoid pathways in plants and fungi remain challenging.
► Bacteria are emerging as prolific producers of diterpenoid natural products.
► Bacterial diterpene synthases are poised to make significant contributions to our understanding of terpenoid biosynthesis.
► Diterpenoid biosynthesis in bacteria provides new opportunities for pathway engineering to produce complex diterpenoid natural products.