The medium-chain fatty acid octanoic acid is an important platform compound widely used in industry. The microbial production from sugars in Saccharomyces cerevisiae is a promising alternative to current non-sustainable production methods, however, titers need to be further increased. To achieve this, it is essential to have in-depth knowledge about the cell physiology during octanoic acid production. To this end, we collected the first RNA-Seq data of an octanoic acid producer strain at three time points during fermentation. The strain produced higher levels of octanoic acid and increased levels of fatty acids of other chain lengths (C6–C18) but showed decreased growth compared to the reference. Furthermore, we show that the here analyzed transcriptomic response to internally produced octanoic acid is notably distinct from a wild type's response to externally supplied octanoic acid as reported in previous publications. By comparing the transcriptomic response of different sampling times, we identified several genes that we subsequently overexpressed and knocked out, respectively. Hereby we identified RPL40B, to date unknown to play a role in fatty acid biosynthesis or medium-chain fatty acid tolerance. Overexpression of RPL40B led to an increase in octanoic acid titers by 40%.

中文翻译：

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酿酒酵母对辛酸产生的转录组学反应

中链脂肪酸辛酸是工业上广泛使用的重要平台化合物。用酿酒酵母中的糖进行微生物生产是目前非可持续生产方法的有希望的替代品，但需要进一步提高滴度。为此，必须深入了解辛酸生产过程中的细胞生理学。为此，我们在发酵过程中的三个时间点收集了辛酸生产菌株的第一个 RNA-Seq 数据。该菌株产生了更高水平的辛酸和更高水平的其他链长（C6-C18）的脂肪酸，但与参考相比显示增长减少。此外，我们表明，此处分析的对内部产生的辛酸的转录组反应与野生型明显不同' s 对以前出版物中报道的外部提供的辛酸的反应。通过比较不同采样时间的转录组响应，我们确定了几个我们随后分别过表达和敲除的基因。因此，我们鉴定了 RPL40B，迄今为止未知其在脂肪酸生物合成或中链脂肪酸耐受中发挥作用。RPL40B 的过表达导致辛酸滴度增加 40%。