酿酒酵母乙酰辅酶A精细调控合成萜类化合物研究进展

Fine-regulation of Saccharomyces cerevisiae acetyl-CoA to synthetize terpenoids

酿酒酵母作为细胞工厂被用来生产多种萜类化合物。乙酰辅酶A为合成萜类化合物的基本前体,细胞质乙酰辅酶A供应不足会导致目标产物产量较低,调控乙酰辅酶A合成是构建目标萜类化合物高产合成途径的重要手段。本文介绍了酿酒酵母乙酰辅酶A作为重要中心碳代谢分子,主要在细胞核组蛋白乙酰化、细胞质丙酮酸脱氢酶支路、线粒体三羧酸循环和过氧化物酶体乙醛酸循环中参与的代谢过程。总结了通过强化酿酒酵母内源丙酮酸脱氢酶支路,引入低三磷酸腺苷(ATP)消耗的异源乙酰辅酶A合成途径,增加辅酶A合成和利用线粒体乙酰辅酶A含量高且对其不渗透的特性进行区域化合成以提高乙酰辅酶A含量的代谢工程策略,旨在为酿酒酵母萜类化合物的高效合成提供借鉴。

Saccharomyces cerevisiae has been engineered as a cell factory for producing terpenoids. Acetyl-CoA is a basic precursor for terpenoid synthesis,but its insufficient supply in cytoplasm may result in a lower yield of desired products. The regulation of acetyl-CoA synthesis is an important means to construct high-yield synthetic pathway for target terpenoids. Therefore,this paper illustrates an important central carbon metabolism molecule acetyl-CoA,which is involved in the metabolism of four different organelles,including nucleus histone acetylation,cytoplasm pyruvate dehydrogenase branch,mitochondria tricarboxylic acid cycle,and peroxisome glyoxylate shunt. The metabolic engineering strategies to improve the content of acetyl-CoA,include strengthening endogenous pyruvate dehydrogenase branch,introducing heterologous acetyl-CoA synthetic pathway with lower ATP input requirement,enhancing CoA synthesis and mitochondrial regionalization of acetyl-CoA,which may be valuable for the efficient production of terpenoids in Saccharomyces cerevisiae.