Key Laboratory of Biomass Chemical Engineering (Education Ministry), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China.
ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311200, China.
J Agric Food Chem. 2023 Jun 14;71(23):9020-9030. doi: 10.1021/acs.jafc.3c01743. Epub 2023 Jun 1.
The vitamin E component δ-tocotrienol has shown impressive activities in radioprotection, neuroprotection, and cholesterol reduction. Its production is limited by the low content in plants and difficulty in separation from other tocotrienols. Fermentative production using a microbial cell factory that exclusively produces and secretes δ-tocotrienol is a promising alternative approach. Assembly of the δ-tocotrienol synthetic pathway in followed by comprehensive pathway engineering led to the production of 73.45 mg/L δ-tocotrienol. Subsequent addition of 2-hydroxypropyl-β-cyclodextrin (CD) and overexpression of the transcription factor PDR1 significantly elevated δ-tocotrienol titer to 241.7 mg/L (63.65 mg/g dry cell weight) in shake flasks, with 30.4% secreted. By properly adding CD and the in situ extractant olive oil, 181.12 mg/L of δ-tocotrienol was collected as an extracellular product, accounting for 85.6% of the total δ-tocotrienol production. This process provides not only a promising δ-tocotrienol cell factory but also insights into yeast engineering toward secretory production of other terpenoids.
生育三烯酚的维生素 E 成分 δ-生育三烯酚在放射防护、神经保护和降低胆固醇方面表现出了令人印象深刻的活性。其产量受到植物中含量低和从其他生育三烯酚中分离困难的限制。使用专门生产和分泌 δ-生育三烯酚的微生物细胞工厂进行发酵生产是一种很有前途的替代方法。在 中组装 δ-生育三烯酚合成途径，然后进行全面的途径工程，导致生产出 73.45mg/L 的 δ-生育三烯酚。随后添加 2-羟丙基-β-环糊精 (CD) 和过表达转录因子 PDR1，显著将 δ-生育三烯酚的产量提高到摇瓶中的 241.7mg/L（63.65mg/g 干细胞重量），其中 30.4%分泌。通过适当添加 CD 和原位提取剂橄榄油，收集到 181.12mg/L 的 δ-生育三烯酚作为细胞外产物，占总 δ-生育三烯酚产量的 85.6%。该工艺不仅为 δ-生育三烯酚提供了一个有前途的细胞工厂，而且为酵母工程向其他萜类化合物的分泌生产提供了思路。
