Encapsulins in Terpene Biosynthesis: Enzyme Nanoreactors in Bacterial Secondary Metabolism.

Encapsulins are self-assembling protein nanocompartments widely distributed across prokaryotes that sequester diverse enzymes. While most encapsulin systems studied thus far are involved in nutrient storage or oxidative stress response, recent bioinformatic and experimental studies have also demonstrated their involvement in secondary metabolism, particularly terpenoid biosynthesis. In this perspective, we first present a comprehensive analysis of Family 2B encapsulin gene clusters likely involved in terpene or terpenoid biosynthetic pathways. We then highlight the structural features of Family 2B encapsulin shells, with a focus on their pore properties and putative ligand-binding domains. We review the mechanisms of enzyme cargo loading in Family 2B systems and examine known examples of terpenoid synthesis compartmentalized within Family 2B encapsulin shells. This is followed by a discussion of the molecular logic and potential functional advantages of enzyme encapsulation. Finally, we consider outstanding questions and future research directions aimed at elucidating the molecular details and physiological implications of encapsulin-mediated bacterial terpene biosynthesis.