Heterologous transporter expression for improved fatty alcohol secretion in yeast
Heterologous transporter expression for improved fatty alcohol secretion in yeast
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DOI：
10.1016/j.ymben.2017.11.008
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发表时间：
2018-01-01
影响因子：
8.4
通讯作者：
Siewers, Verena
中科院分区：
文献类型：
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作者：
Hu, Yating;Zhu, Zhiwei;Siewers, Verena
酵母酿酒酵母（Saccharomyces cerevisiae）是用于工业规模生产生物燃料（包括脂肪醇）的有吸引力的宿主，这是由于其对苛刻发酵条件的稳健性和耐受性。许多代谢工程策略已被应用于产生高级脂肪醇的菌株。然而，脂肪醇积累导致的生长受损和提取成本高是限制大规模生产的因素。在这里，我们证明了使用异源转运蛋白是一种很有前途的策略，以增加脂肪醇的生产。在测试的几种植物和哺乳动物转运蛋白中，人FATP 1显示在高脂肪醇生产酵母菌株中介导脂肪醇输出。实现了脂肪醇分泌的约五倍增加。结果表明，整体细胞适应性受益于脂肪醇分泌，并且FATP 1的酰基辅酶A合酶活性也有助于增加细胞生长。这是第一项通过在酵母中表达异源转运蛋白来增加细胞对脂肪醇生产的适应性的研究，这项研究表明了FATP 1的新的潜在功能，迄今为止，FATP 1一直被认为是游离脂肪酸的输入者。我们还成功地确定了FATP 1的功能结构域参与脂肪醇的输出，通过FATP 1和另一个转运蛋白，FATP 4之间的结构域交换。这项研究可能有助于在酵母中成功商业化生产脂肪醇，并启发新型细胞工厂的设计。
The yeast Saccharomyces cerevisiae is an attractive host for industrial scale production of biofuels including fatty alcohols due to its robustness and tolerance towards harsh fermentation conditions. Many metabolic engineering strategies have been applied to generate high fatty alcohol production strains. However, impaired growth caused by fatty alcohol accumulation and high cost of extraction are factors limiting large-scale production. Here, we demonstrate that the use of heterologous transporters is a promising strategy to increase fatty alcohol production. Among several plant and mammalian transporters tested, human FATP1 was shown to mediate fatty alcohol export in a high fatty alcohol production yeast strain. An approximately five-fold increase of fatty alcohol secretion was achieved. The results indicate that the overall cell fitness benefited from fatty alcohol secretion and that the acyl-CoA synthase activity of FATP1 contributed to increased cell growth as well. This is the first study that enabled an increased cell fitness for fatty alcohol production by heterologous transporter expression in yeast, and this investigation indicates a new potential function of FATP1, which has been known as a free fatty acid importer to date. We furthermore successfully identified the functional domain of FATP1 involved in fatty alcohol export through domain exchange between FATP1 and another transporter, FATP4. This study may facilitate a successful commercialization of fatty alcohol production in yeast and inspire the design of novel cell factories.