Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland and Helmholtz Centre for Infection Research, Saarbrücken, Germany.
Institute for Systems Biotechnology, Saarland University, Saarbrücken, Germany.
Nat Commun. 2019 Sep 6;10(1):4055. doi: 10.1038/s41467-019-12025-8.
Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly the omega-3 LC-PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), have been associated with beneficial health effects. Consequently, sustainable sources have to be developed to meet the increasing demand for these PUFAs. Here, we demonstrate the design and construction of artificial PUFA biosynthetic gene clusters (BGCs) encoding polyketide synthase-like PUFA synthases from myxobacteria adapted for the oleaginous yeast Yarrowia lipolytica. Genomic integration and heterologous expression of unmodified or hybrid PUFA BGCs yielded different yeast strains with specific LC-PUFA production profiles at promising yield and thus valuable for the biotechnological production of distinct PUFAs. Nutrient screening revealed a strong enhancement of PUFA production, when cells were phosphate limited. This represents, to the best of our knowledge, highest concentration of DHA (16.8 %) in total fatty acids among all published PUFA-producing Y. lipolytica strains.
长链多不饱和脂肪酸（LC-PUFAs），特别是 omega-3 LC-PUFAs 二十碳五烯酸（EPA）、二十二碳五烯酸（DPA）和二十二碳六烯酸（DHA），与有益的健康效果有关。因此，必须开发可持续的来源来满足这些 PUFA 的日益增长的需求。在这里，我们展示了人工 PUFA 生物合成基因簇（BGC）的设计和构建，这些基因簇编码了适应产油酵母解脂耶氏酵母的粘细菌中的聚酮合酶样 PUFA 合酶。未修饰或杂交的 PUFA BGC 的基因组整合和异源表达产生了不同的酵母菌株，具有有前途的产率和特定的 LC-PUFA 生产谱，因此对于生物技术生产不同的 PUFA 具有重要价值。营养物筛选表明，当细胞受到磷酸盐限制时，PUFA 的产量会大幅提高。据我们所知，这是所有已发表的产 PUFA 的解脂耶氏酵母菌株中总脂肪酸中 DHA（16.8%）浓度最高的一次。
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