Abstract：
Vitamin B5, also called d-pantothenic acid, is an essential vitamin in the human body and is widely used in pharmaceuticals, nutritional supplements, food, and cosmetics. However, few studies have investigated the microbial production of d-pantothenic acid, especially in Saccharomyces cerevisiae. By employing a systematic optimization strategy, we screened seven key genes in d-pantothenic acid biosynthesis from diverse species, including bacteria, yeast, fungi, algae, plants, animals, etc., and constructed an efficient heterologous d-pantothenic acid pathway in S. cerevisiae. By adjusting the copy number of the pathway modules, knocking out the endogenous bypass gene, balancing NADPH utilization, and regulating the GAL inducible system, a high-yield d-pantothenic acid-producing strain, DPA171, which can regulate gene expression using glucose, was constructed. By optimizing fed-batch fermentation, DPA171 produced 4.1 g/L d-pantothenic acid, which is the highest titer in S. cerevisiae to date. This study provides guidance for the development of vitamin B5 microbial cell factories.
摘要：
维生素B5，也称为d-泛酸，是人体必需的维生素，广泛用于制药，营养补充剂,食物,和化妆品。然而,很少有研究调查微生物生产d-泛酸，尤其是在酿酒酵母中。通过采用系统的优化策略，我们从不同物种中筛选了7个D-泛酸生物合成的关键基因，包括细菌,酵母，真菌,藻类,植物,动物,等。,并在酿酒酵母中构建了高效的异源d-泛酸途径。通过调整通路模块的拷贝数，敲除内源性旁路基因，平衡NADPH利用率，调节GAL诱导系统，高产d-泛酸菌株，DPA171，它可以使用葡萄糖调节基因表达，是建造的。通过优化补料分批发酵，DPA171产生4.1克/升d-泛酸，这是迄今为止酿酒酵母中的最高滴度。本研究为维生素B5微生物细胞工厂的开发提供了指导。
