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用于 L-苹果酸生产的代谢工程。

Metabolic Engineering of for l-Malic Acid Production.

机构信息

State Key Lab of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.

出版信息

J Agric Food Chem. 2023 Mar 8;71(9):4043-4050. doi: 10.1021/acs.jafc.2c09078. Epub 2023 Feb 22.

Abstract

l-Malic acid has various applications in the chemical and food industries. The filamentous fungus is known to be an efficient enzyme producer. Here, through metabolic engineering, was constructed for the first time as an excellent cell factory for l-malic acid production. The heterologous overexpression of genes encoding the C4-dicarboxylate transporter from and initiated l-malic acid production. The overexpression of pyruvate carboxylase from in the reductive tricarboxylic acid pathway further increased both the titer and yield of l-malic acid, resulting in the highest titer reported in a shake-flask culture. Furthermore, the deletion of malate thiokinase blocked l-malic acid degradation. Finally, the engineered strain produced 220.5 g/L of l-malic acid in a 5 L fed-batch culture (productivity of 1.15 g/L/h). A cell factory was created for the efficient production of l-malic acid.

摘要

L-苹果酸在化学和食品工业中有多种应用。丝状真菌被认为是一种高效的酶产生菌。在这里,通过代谢工程,首次构建了作为生产 L-苹果酸的优良细胞工厂。异源过表达来自 和 的 C4-二羧酸转运蛋白基因启动了 L-苹果酸的生产。来自 的丙酮酸羧化酶在还原三羧酸途径中的过表达进一步提高了 L-苹果酸的产量和得率,在摇瓶培养中达到了报道的最高产量。此外,苹果酸硫激酶的缺失阻止了 L-苹果酸的降解。最后,工程菌在 5 L 分批补料培养中生产了 220.5 g/L 的 L-苹果酸(生产强度为 1.15 g/L/h)。为高效生产 L-苹果酸创建了一个 细胞工厂。

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