Chai Liang, Che Jiaxin, Qi Qingsheng, Hou Jin
State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, P. R. China.
J Agric Food Chem. 2024 Dec 18;72(50):27715-27725. doi: 10.1021/acs.jafc.4c09608. Epub 2024 Dec 3.
Squalene is a linear polyunsaturated triterpene which has multiple physiological functions including anticancer, antioxidant, and skin-care. It has been widely used in the food, medicine, and cosmetics sectors and also serves as a precursor of triterpenes and steroids. Recently, the production of squalene by microbial cell hosts has drawn much attention due to its sustainability, environmental friendliness, and great efficiency. In this review, we first introduce the recent developments in the production of squalene by employing microbial cell factories, especially yeasts. Next, we underscore the primary metabolic strategies, including the biosynthetic pathway engineering, precursor manipulation, cofactor engineering, and organelle engineering. In addition to traditional metabolic engineering strategies, we also discuss some prospective metabolic regulation approaches, including regulation of lipid synthesis, identifying and manipulating related transcription factors, dynamic regulation of the metabolic pathway, and secretion engineering of membrane-impermeable terpenoids. These approaches provide insights for further metabolic engineering of squalene and related terpenoids.
角鲨烯是一种线性多不饱和三萜，具有多种生理功能，包括抗癌、抗氧化和护肤。它已广泛应用于食品、医药和化妆品领域，也是三萜和类固醇的前体。近年来，利用微生物细胞宿主生产角鲨烯因其可持续性、环境友好性和高效性而备受关注。在本综述中，我们首先介绍了利用微生物细胞工厂，特别是酵母生产角鲨烯的最新进展。接下来，我们强调了主要的代谢策略，包括生物合成途径工程、前体操纵、辅因子工程和细胞器工程。除了传统的代谢工程策略外，我们还讨论了一些前瞻性的代谢调控方法，包括脂质合成的调控、相关转录因子的鉴定和操纵、代谢途径的动态调控以及膜不透性萜类化合物的分泌工程。这些方法为角鲨烯和相关萜类化合物的进一步代谢工程提供了思路。
