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.

中文翻译：

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通过合成生物学方法扩大萜烯的结构多样性


萜类化合物表现出化学和结构多样性以及重要的生物活性。尽管它们具有极大的可变性，但这些结构的范围受到通常源自可相互转化的五碳 (C5) 异戊二烯单元的天然产物范围的限制。最近开发了新方法来扩大其结构多样性。本综述系统地探讨了通过经典甲羟戊酸 (MVA) 途径和 C-甲基转移酶 (C-MT) 的共表达，或通过使用鳞翅目甲羟戊酸 (LMVA) 途径的非经典构建模块的组合生物合成。非天然萜类化合物可以通过化学生物学合成和人工金属酶 (ArM) 的萜烯环丙烷化从法尼基二磷酸 (FPP) 类似物中产生。讨论了加速萜烯生物合成的先进技术。该综述为增加有价值的萜类化合物及其衍生物的多样性以及扩大其潜在应用提供了有价值的参考。