Expanding the structural diversity of terpenes by synthetic biology approaches

Terpenoids display chemical and structural diversities as well as important biological activities. Despite their extreme variability, the range of these structures is limited by the scope of natural products that canonically derive from interconvertible five-carbon (C5) isoprene units. New approaches have recently been developed to expand their structural diversity. This review systematically explores the combinatorial biosynthesis of noncanonical building blocks via the coexpression of the canonical mevalonate (MVA) pathway and C-methyltransferases (C-MTs), or by using the lepidopteran mevalonate (LMVA) pathway. Unnatural terpenoids can be created from farnesyl diphosphate (FPP) analogs by chemobiological synthesis and terpene cyclopropanation by artificial metalloenzymes (ArMs). Advanced technologies to accelerate terpene biosynthesis are discussed. This review provides a valuable reference for increasing the diversity of valuable terpenoids and their derivatives, as well as for expanding their potential applications.