Yarrowia lipolytica has emerged as an important non-model host for terpene production. However, three main challenges remain in industrial production using this yeast. First, considerable knowledge gaps exist in metabolic flux across multiple compartments, cofactor generation, and catabolism of non-sugar carbon sources. Second, many enzymatic steps in the complex-terpene synthesis pathway can pose rate-limitations, causing accumulation of toxic intermediates and increased metabolic burdens. Third, metabolic shifts, morphological changes, and genetic mutations are poorly characterized under industrial fermentation conditions. To overcome these challenges, systems metabolic analysis, protein engineering, novel pathway engineering, model-guided strain design, and fermentation optimization have been attempted with some successes. Further developments that address these challenges are needed to advance the Yarrowia lipolytica platform for industrial-scale production of high-value terpenes, including those with highly complex structures such as anticancer molecules withanolides and insecticidal limonoids.

中文翻译：

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使用非模型酵母解脂耶氏酵母生物合成萜烯化合物：重大挑战和一些观点。

解脂耶氏酵母已成为萜烯生产的重要非模型宿主。然而，在使用这种酵母的工业生产中仍然存在三个主要挑战。首先，在跨多个区室的代谢通量、辅因子生成和非糖碳源的分解代谢方面存在相当大的知识差距。其次，复合萜烯合成途径中的许多酶促步骤会限制速率，导致有毒中间体的积累和代谢负担的增加。第三，在工业发酵条件下，代谢变化、形态变化和基因突变的特征很差。为了克服这些挑战，系统代谢分析、蛋白质工程、新途径工程、模型引导的菌株设计和发酵优化已经尝试并取得了一些成功。