Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, School of Pharmacy, School of Public Health, Hangzhou Normal University, Hangzhou 310000, China; Joint BioEnergy Institute, Emeryville, CA 94608, USA.
Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, School of Pharmacy, School of Public Health, Hangzhou Normal University, Hangzhou 310000, China.
Trends Biotechnol. 2024 Jun;42(6):699-713. doi: 10.1016/j.tibtech.2023.12.006. Epub 2024 Jan 16.
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.
萜类化合物具有化学和结构多样性以及重要的生物活性。尽管它们具有极端的可变性，但这些结构的范围受到天然产物的限制，这些天然产物通常源自可相互转化的五个碳（C5）异戊二烯单元。最近开发了新方法来扩大它们的结构多样性。本文系统地探讨了通过共表达经典的甲羟戊酸（MVA）途径和 C-甲基转移酶（C-MTs），或使用鳞翅目甲羟戊酸（LMVA）途径来组合生物合成非典型构建块。通过化学生物合成和人工金属酶（ArMs）的萜类环丙烷化，可以从未法尼二磷酸（FPP）类似物中产生非天然萜类化合物。讨论了加速萜类生物合成的先进技术。本文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。
