Engineering Critical Enzymes and Pathways for Improved Triterpenoid Biosynthesis in Yeast.,ACS Synthetic Biology

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Engineering Critical Enzymes and Pathways for Improved Triterpenoid Biosynthesis in Yeast.
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2020-08-07 , DOI: 10.1021/acssynbio.0c00124
Hao Guo ₁ , Huiyan Wang ₁ , Yi-Xin Huo _{1,

2,

3}

Affiliation

Triterpenoids represent a diverse group of phytochemicals that are widely distributed in the plant kingdom and have many biological activities. The heterologous production of triterpenoids in Saccharomyces cerevisiae has been successfully implemented by introducing various triterpenoid biosynthetic pathways. By engineering related enzymes as well as through yeast metabolism, the yield of various triterpenoids is significantly improved from the milligram per liter scale to the gram per liter scale. This achievement demonstrates that engineering critical enzymes is considered a potential strategy to overcome the main hurdles of the industrial application of these potent natural products. Here, we review strategies for designing enzymes to improve the yield of triterpenoids in S. cerevisiae in terms of three main aspects: 1, elevating the supply of the precursor 2,3-oxidosqualene; 2, optimizing triterpenoid-involved reactions; and 3, lowering the competition of the native sterol pathway. Then, we provide challenges and prospects for further enhancing triterpenoid production in S. cerevisiae.

中文翻译：

改进酵母中三萜生物合成的工程关键酶和途径。

三萜类化合物代表了广泛分布于植物界并具有多种生物活性的多种植物化学物质。通过引入各种三萜类生物合成途径，已成功实现了酿酒酵母中三萜类化合物的异源生产。通过工程化相关酶以及通过酵母代谢，各种三萜的产量从毫克每升规模显着提高到克每升规模。这一成就表明，工程关键酶被认为是克服这些有效天然产物工业应用主要障碍的潜在策略。在这里，我们回顾了设计酶以提高酿酒酵母中三萜类化合物产量的策略主要从三个方面来看： 1、提高前体2,3-氧化角鲨烯的供应量；2、优化三萜参与反应；3、降低天然甾醇途径的竞争。然后，我们提供了进一步提高酿酒酵母中三萜类化合物产量的挑战和前景。

更新日期：2020-09-20

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