Li Ning, Zeng Weizhu, Zhou Jingwen, Xu Sha
National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, China.
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, China.
Biotechnol Biofuels Bioprod. 2022 Mar 14;15(1):27. doi: 10.1186/s13068-022-02114-0.
O-Acetyl-L-homoserine (OAH) is an important potential platform chemical. However, low levels of production of OAH are greatly limiting its industrial application. Furthermore, as a common and safe amino acid-producing strain, Corynebacterium glutamicum has not yet achieved efficient production of OAH.
First, exogenous L-homoserine acetyltransferase was introduced into an L-homoserine-producing strain, resulting in the accumulation of 0.98 g/L of OAH. Second, by comparing different acetyl-CoA biosynthesis pathways and adding several feedstocks (acetate, citrate, and pantothenate), the OAH titer increased 2.3-fold to 3.2 g/L. Then, the OAH titer further increased by 62.5% when the expression of L-homoserine dehydrogenase and L-homoserine acetyltransferase was strengthened via strong promoters. Finally, the engineered strain produced 17.4 g/L of OAH in 96 h with acetate as the supplementary feedstock in a 5-L bioreactor.
This is the first report on the efficient production of OAH with C. glutamicum as the chassis, which would provide a good foundation for industrial production of OAH.
O-乙酰-L-高丝氨酸（OAH）是一种重要的潜在平台化学品。然而，OAH的低产量极大地限制了其工业应用。此外，作为一种常见且安全的氨基酸生产菌株，谷氨酸棒杆菌尚未实现OAH的高效生产。
首先，将外源L-高丝氨酸乙酰转移酶引入一株L-高丝氨酸生产菌株中，积累了0.98 g/L的OAH。其次，通过比较不同的乙酰辅酶A生物合成途径并添加几种原料（乙酸盐、柠檬酸盐和泛酸盐），OAH的滴度提高了2.3倍，达到3.2 g/L。然后，当通过强启动子增强L-高丝氨酸脱氢酶和L-高丝氨酸乙酰转移酶的表达时，OAH滴度进一步提高了62.5%。最后，在5-L生物反应器中，以乙酸盐作为补充原料，工程菌株在96小时内产生了17.4 g/L的OAH。
这是以谷氨酸棒杆菌为底盘高效生产OAH的首次报道，将为OAH的工业化生产提供良好基础。
