Engineering Escherichia coli for Efficient De Novo Synthesis of Salidroside

IF 5.7 1区 农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY
Weizhu Zeng, Huijing Wang, Jianbin Chen, Minglong Hu, Xinru Wang, Jian Chen, Jingwen Zhou
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Abstract

Salidroside is a high-value plant-derived glycoside with diverse biological activities, but the main industrial salidroside production method, extraction from Rhodiola plants, is insufficient to meet the growing market demand. The biosynthetic route via microbial fermentation is a sustainable and eco-friendly alternative method. De novo synthesis of the precursor tyrosol was established by introducing the ARO10 and ADH6 genes. Systematic metabolic engineering resulted in 3.0 g/L tyrosol, but accumulated tyrosol inhibited cell growth. Adaptive evolution produced an evolved strain with a 10.0% higher OD600 and a 3.3 g/L tyrosol titer. Introducing glucosyltransferase AtUGT85A1, and overexpressing phosphoglucose mutase pgm and UDP-glucose pyrophosphorylase galU, achieved de novo synthesis of salidroside. Furthermore, AtUGT85A1 was semirationally engineered, resulting in the A21G mutation, which enhanced salidroside production by 31.2%. The optimally engineered strain produced 16.8 g/L salidroside with 0.4 g/(L h) productivity in a 5 L bioreactor. This study laid a foundation for future industrial production of salidroside and provided important guidance for efficient biosynthesis of other tyrosol derivatives.

Abstract Image

高效从头合成红景天苷的工程大肠杆菌
红景天苷是一种具有多种生物活性的高价值植物源糖苷,但目前主要的工业红景天苷生产方法——从红景天植物中提取红景天苷已不能满足日益增长的市场需求。通过微生物发酵的生物合成途径是一种可持续和环保的替代方法。通过引入ARO10和ADH6基因,建立了前体酪醇的从头合成。系统代谢工程产生3.0 g/L的酪醇,但累积的酪醇抑制细胞生长。适应性进化产生的进化菌株OD600提高10.0%,酪醇滴度为3.3 g/L。引入葡萄糖基转移酶AtUGT85A1,过表达磷酸葡萄糖突变酶pgm和udp -葡萄糖焦磷酸化酶galU,实现了红柳苷的从头合成。此外,对AtUGT85A1进行半基因工程改造,产生A21G突变,使红景天苷的产量提高了31.2%。优化后的菌株在5l生物反应器中以0.4 g/(L h)的生产率生产16.8 g/L红景天苷。该研究为红景天苷的工业化生产奠定了基础,并为其他酪醇衍生物的高效生物合成提供了重要指导。
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来源期刊
Journal of Agricultural and Food Chemistry
Journal of Agricultural and Food Chemistry 农林科学-农业综合
CiteScore
9.90
自引率
8.20%
发文量
1375
审稿时长
2.3 months
期刊介绍: The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.
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