Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, Gothenburg SE-41296, Sweden.
Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Gothenburg SE-41296, Sweden.
Nat Commun. 2017 May 26;8:15587. doi: 10.1038/ncomms15587.
Production of chemicals and biofuels through microbial fermentation is an economical and sustainable alternative for traditional chemical synthesis. Here we present the construction of a Saccharomyces cerevisiae platform strain for high-level production of very-long-chain fatty acid (VLCFA)-derived chemicals. Through rewiring the native fatty acid elongation system and implementing a heterologous Mycobacteria FAS I system, we establish an increased biosynthesis of VLCFAs in S. cerevisiae. VLCFAs can be selectively modified towards the fatty alcohol docosanol (CHO) by expressing a specific fatty acid reductase. Expression of this enzyme is shown to impair cell growth due to consumption of VLCFA-CoAs. We therefore implement a dynamic control strategy for separating cell growth from docosanol production. We successfully establish high-level and selective docosanol production of 83.5 mg l in yeast. This approach will provide a universal strategy towards the production of similar high value chemicals in a more scalable, stable and sustainable manner.
通过微生物发酵生产化学品和生物燃料是一种经济且可持续的替代传统化学合成的方法。在这里，我们构建了一个用于生产高浓度的基于超长链脂肪酸（VLCFA）的化学品的酿酒酵母平台菌株。通过重新布线天然脂肪酸延长系统并实施异源分枝杆菌 FAS I 系统，我们在酿酒酵母中建立了 VLCFA 的增加生物合成。VLCFAs 可以通过表达特定的脂肪酸还原酶选择性地修饰为脂肪醇二十四烷醇（CHO）。表达这种酶会由于消耗 VLCFA-CoAs 而损害细胞生长。因此，我们实施了一种动态控制策略，将细胞生长与二十四烷醇生产分离。我们成功地在酵母中建立了 83.5mg/L 的高水平和选择性的二十四烷醇生产。这种方法将为以更具可扩展性、稳定性和可持续性的方式生产类似高价值化学品提供一种通用策略。
