Jiao Xue, Shen Bin, Li Min, Ye Lidan, Yu Hongwei
Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
Zhejiang University-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311200, China.
ACS Synth Biol. 2022 Feb 18;11(2):788-799. doi: 10.1021/acssynbio.1c00484. Epub 2022 Jan 31.
Tocotrienols as important components of vitamin E have attracted increasing attention, with recent progress made in their heterologous biosynthesis, but all as intracellular products. Aiming to further improve the tocotrienol production capacity of engineered yeast and to advance toward industrial fermentation of tocotrienols, we first optimized the synthetic pathway to enhance the tocotrienol yield and then attempted to realize their secretory production by exploring biphasic extractive fermentation conditions and screening for endogenous transporters. Finally, a strain with tocotrienol yield of 25.57 mg/g dry cell weight was generated, and the tocotrienol titer reached 82.68 mg/L in shake-flask cultures, with 73.66% of the product secreted into the organic phase. For the first time, we have reported that the vitamin E components could be harvested as extracellular products of microbial cell factories, which could largely simplify the downstream process and could be of significance for fermentative production of these products.
生育三烯酚作为维生素E的重要组成部分，已引起越来越多的关注，其异源生物合成最近取得了进展，但都是作为细胞内产物。为了进一步提高工程酵母的生育三烯酚生产能力并朝着生育三烯酚的工业发酵迈进，我们首先优化了合成途径以提高生育三烯酚产量，然后通过探索双相萃取发酵条件和筛选内源性转运蛋白来尝试实现其分泌生产。最终，获得了一株生育三烯酚产量为25.57 mg/g干细胞重量的菌株，在摇瓶培养中生育三烯酚滴度达到82.68 mg/L，其中73.66%的产物分泌到有机相中。我们首次报道了维生素E成分可以作为微生物细胞工厂的细胞外产物收获，这可以大大简化下游工艺，并且对于这些产物的发酵生产具有重要意义。
