L-Phenylacetylcarbinol (L-PAC) which is used as a precursor for the production of ephedrine and pseudoephedrine is the first reported biologically produced α-hydroxy ketone compound. l-PAC is commercially produced by the yeast Saccharomyces cerevisiae. Yeast cells transform exogenously added benzaldehyde into l-PAC by using the action of pyruvate decarboxylase (PDC) enzyme. In this work, genome-scale model and flux balance analysis were used to identify novel target genes for the enhancement of l-PAC production in yeast. The effect of gene deletions on the flux distributions in the metabolic model of S. cerevisiae was assessed using OptGene and minimization of metabolic adjustments. Six single gene deletion strains, namely Δrpe1, Δpda1, Δadh3, Δadh1, Δzwf1 and Δpdc1, were predicted in silico and further tested in vivo by using knock-out strains cultivated semi-anaerobically on glucose and benzaldehyde as substrates. Δzwf1 mutant exhibited the highest l-PAC formation (2.48 g/L) by using 2 g/L of benzaldehyde which is equivalent to 88 % of the theoretical yield.

中文翻译：

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通过计算机辅助代谢工程提高酿酒酵母中的l-苯基乙酰基甲醇生产。

用作生产麻黄碱和伪麻黄碱的前体的L-苯基乙酰基甲醇（L-PAC）是第一个报道的生物学上生产的α-羟基酮化合物。1-PAC是由酿酒酵母酵母生产的。酵母细胞通过丙酮酸脱羧酶（PDC）的作用将外源添加的苯甲醛转化为1-PAC。在这项工作中，使用基因组规模模型和通量平衡分析来鉴定新的靶基因以增强酵母中l-PAC的产生。使用OptGene和最小化代谢调节来评估基因缺失对酿酒酵母代谢模型中通量分布的影响。六个单基因缺失菌株，分别为Δrpe1，Δpda1，Δadh3，Δadh1，Δzwf1和Δpdc1，可以通过计算机模拟预测，并通过使用以葡萄糖和苯甲醛为底物半厌氧培养的敲除菌株在体内进行进一步测试。通过使用2 g / L的苯甲醛，Δzwf1突变体表现出最高的l-PAC形成（2.48 g / L），相当于理论收率的88％。