Li Haibo, Alper Hal S
Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX, USA.
McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Biotechnol J. 2016 Sep;11(9):1230-40. doi: 10.1002/biot.201600210. Epub 2016 Jul 14.
The conversion of lignocellulosic sugars, in particular xylose, is important for sustainable fuels and chemicals production. While the oleaginous yeast Yarrowia lipolytica is a strong candidate for lipid production, it is currently unable to effectively utilize xylose. By introducing a heterologous oxidoreductase pathway and enabling starvation adaptation, we obtained a Y. lipolytica strain, E26 XUS, that can use xylose as a sole carbon source and produce over 15 g/L of lipid in bioreactor fermentations (29.3% of theoretical yield) with a maximal lipid productivity of 0.19 g/L/h. Genomic sequencing and genetic analysis pointed toward increases in genomic copy number of the pathway and resulting elevated expression levels as the causative mutations underlying this improved phenotype. More broadly, many regions of the genome were duplicated during starvation of Yarrowia. This strain can form the basis for further engineering to enhance xylose catabolic rates and conversion. Finally, this study also reveals the flexibility and dynamic nature of the Y. lipolytica genome, and the means at which starvation can be used to induce genomic duplications.
木质纤维素糖（尤其是木糖）的转化对于可持续燃料和化学品生产至关重要。虽然产油酵母解脂耶氏酵母是脂质生产的有力候选者，但它目前无法有效利用木糖。通过引入异源氧化还原酶途径并实现饥饿适应，我们获得了一株解脂耶氏酵母菌株E26 XUS，它可以将木糖作为唯一碳源，并在生物反应器发酵中产生超过15 g/L的脂质（理论产量的29.3%），最大脂质生产率为0.19 g/L/h。基因组测序和遗传分析表明，该途径基因组拷贝数的增加以及由此导致的表达水平升高是这种改良表型的致病突变。更广泛地说，在解脂耶氏酵母饥饿期间，基因组的许多区域发生了复制。该菌株可为进一步工程改造以提高木糖分解代谢速率和转化率奠定基础。最后，这项研究还揭示了解脂耶氏酵母基因组的灵活性和动态性质，以及利用饥饿诱导基因组复制的方法。
