Decompartmentalization of the yeast mitochondrial metabolism to improve chemical production in Issatchenkia orientalis

• 全文链接

东方伊萨酵母线粒体代谢的去区隔化改造以提高化学品合成能力

关键词：

来源：

Nature Communications

全文链接：

//agri.nais.net.cn/topic/downloadFile/408df911-48ba-4efd-9c7e-ca607af9be77

来源地址：

https://www.nature.com/articles/s41467-025-62304-w

资源所属：

饲料用酶工程

类型：

学术文献

语种：

英语

原文发布日期：

2025-08-02

摘要：

Microbial production of chemicals may suffer from inadequate cofactor provision, a challenge further exacerbated in yeasts due to compartmentalized cofactor metabolism. Here, we perform cofactor engineering through the decompartmentalization of mitochondrial metabolism to improve succinic acid (SA) production in Issatchenkia orientalis. We localize the reducing equivalents of mitochondrial NADH to the cytosol through cytosolic expression of its pyruvate dehydrogenase (PDH) complex and couple a reductive tricarboxylic acid pathway with a glyoxylate shunt, partially bypassing an NADH-dependent malate dehydrogenase to conserve NADH. Cytosolic SA production reaches a titer of 104 g/L and a yield of 0.85 g/g glucose, surpassing the yield of 0.66 g/g glucose constrained by cytosolic NADH availability. Additionally, expressing cytosolic PDH, we expand our I. orientalis platform to enhance acetyl-CoA-derived citramalic acid and triacetic acid lactone production by 1.22- and 4.35-fold, respectively. Our work establishes I. orientalis as a versatile platform to produce markedly reduced and acetyl-CoA-derived chemicals.