Engineering Yarrowia lipolytica for Efficient Synthesis of Geranylgeraniol,Journal of Agricultural and Food Chemistry

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Engineering Yarrowia lipolytica for Efficient Synthesis of Geranylgeraniol
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-06 , DOI: 10.1021/acs.jafc.4c06749
Kaifeng Wang ₁ , Mingxue Yin ₁ , Mei-Li Sun ₁ , Quanyu Zhao ₂ , Rodrigo Ledesma-Amaro ₃ , Xiao-Jun Ji ₁ , Lu Lin ₁

Affiliation

Geranylgeraniol (GGOH) is a crucial component in fragrances and essential oils, and a valuable precursor of vitamin E. It is primarily extracted from the oleoresin of Bixa orellana, but is challenged by long plant growth cycles, severe environmental pollution, and low extraction efficiency. Chemically synthesized GGOH typically comprises a mix of isomers, making the separation process both challenging and costly. Advancements in synthetic biology have enabled the construction of microbial cell factories for GGOH production. In this study, Yarrowia lipolytica was engineered to efficiently synthesize GGOH by expressing heterologous phosphatase genes, enhancing precursor supplies of farnesyl diphosphate, geranylgeranyl pyrophosphate, and acetyl-CoA, and downregulating the squalene synthesis pathway by promoter engineering. Additionally, optimizing fermentation conditions and reducing reactive oxygen species significantly increased the GGOH titer to 3346.47 mg/L in a shake flask. To the best of our knowledge, this is the highest reported GGOH titer in shaking flasks to date, setting a new benchmark for terpenoid production.

中文翻译：

工程化解脂耶氏酵母用于高效合成香叶基香叶醇

香叶基香叶醇（GGOH）是香料和精油的重要成分，也是维生素E的重要前体。它主要从红木的油树脂中提取，但受到植物生长周期长、环境污染严重和提取效率低的挑战。化学合成的 GGOH 通常包含异构体的混合物，使得分离过程既具有挑战性又成本高昂。合成生物学的进步使得用于 GGOH 生产的微生物细胞工厂的建设成为可能。在本研究中，解脂耶氏酵母通过表达异源磷酸酶基因，增强法尼基二磷酸、香叶基香叶基焦磷酸和乙酰辅酶A的前体供应，并通过启动子工程下调角鲨烯合成途径，从而有效合成GGOH。此外，优化发酵条件并减少活性氧，使摇瓶中的 GGOH 滴度显着提高至 3346.47 mg/L。据我们所知，这是迄今为止报道的摇瓶中 GGOH 滴度的最高值，为萜类化合物生产设立了新基准。

更新日期：2024-09-06

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