Development of isopentenyl phosphate kinases and their application in terpenoid biosynthesis

As the largest class of natural products, terpenoids (>90,000) have multiple biological activities and a wide range of applications (e.g., pharmaceutical, agricultural, personal care and food industries). Therefore, the sustainable production of terpenoids by microorganisms is of great interest. Microbial terpenoid production depends on two common building blocks: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). In addition to the natural biosynthetic pathways, mevalonate and methyl-D-erythritol-4-phosphate pathways, IPP and DMAPP can be produced through the conversion of isopentenyl phosphate and dimethylallyl monophosphate by isopentenyl phosphate kinases (IPKs), offering an alternative route for terpenoid biosynthesis. This review summarizes the properties and functions of various IPKs, novel IPP/DMAPP synthesis pathways involving IPKs, and their applications in terpenoid biosynthesis. Furthermore, we have discussed strategies to exploit novel pathways and unleash their potential for terpenoid biosynthesis.