酿酒酵母中萜类化合物的生物合成与代谢调控研究进展

Advances in the biosynthesis and metabolic regulation of terpenoids in Saccharomyces cerevisiae

摘要:

萜类化合物是含量最丰富的一类天然化合物，因其种类繁多、生物活性多样，被广泛应用于食品、医药、化工以及新型燃料等领域。萜类化合物的开发利用价值极高，但依靠植物提取和化学合成等传统生产方式很难满足目前的市场需求。随着合成生物学和代谢工程的发展，构建高效的微生物细胞工厂，特别是以酵母为宿主的细胞工厂，为萜类化合物的大规模生产提供了可能。近年来，研究人员已成功构建出多种萜类化合物的酿酒酵母(Saccharomyces cerevisiae)工程菌株，并通过合成生物学和代谢调控等方法有效提高了目标产物的产量。本文总结了近几年利用 S. cerevisiae底盘细胞生物合成萜类化合物的具体实例，阐述了对S. cerevisiae生产萜类化合物的调控策略：包括代谢途径构建与优化、关键酶的挖掘与改造、辅因子再生工程、细胞区室化工程、细胞外排工程，以及细胞耐受性改造等，为进一步利用S. cerevisiae细胞工厂合成更多更高产量的萜类化合物提供参考。

关键词:酿酒酵母;萜类化合物;生物合成;代谢调控

Abstract:

Terpenoids are the one of most abundant natural products. With diverse varieties and biological activities, they are widely used in the food, medicine, chemical industry, and novel fuels. However, the conventional methods such as plant extraction and chemical synthesis cannot meet the current market demand for terpenoids. Efficient microbial cell factories, especially engineered Saccharomyces cerevisiae strains, have been constructed for the industrial production of terpenoids. In recent years, researchers have constructed multiple S. cerevisiae strains with increased yield and productivity via approaches of synthetic biology and metabolic engineering. This paper reviews the recent progress in the biosynthesis of terpenoids in S. cerevisiae cells and summarizes a variety of metabolic engineering strategies for the production of terpenoids in S. cerevisiae. These strategies include the construction and optimization of metabolic pathways, the mining and modification of key enzymes, the regeneration of cofactors, the engineering of cell localization and cell efflux, and the improvement of cell tolerance. Our review will provide information and strategies for the effective biosynthesis of terpenoids in S. cerevisiae.

Key words:Saccharomyces cerevisiae;terpenoids;biosynthesis;metabolic regulation