As an important active ingredient in the rare Chinese herb Gastrodiae Rhizoma and also the main precursor for gastrodin biosynthesis, 4-hydroxybenzyl alcohol has multiple pharmacological activities such as anti-inflammation, anti-tumor, and anti-cerebral ischemia. The pharmaceutical products with 4-hydroxybenzyl alcohol as the main component have been increasingly favored. At present, 4-hydroxybenzyl alcohol is mainly obtained by natural extraction and chemical synthesis, both of which, however, exhibit some shortcomings that limit the long-term application of 4-hydroxybenzyl alcohol. The wild and cultivated Gastrodia elata resources are limited. The chemical synthesis requires many steps, long time, and harsh reaction conditions. Besides, the resulting by-products are massive and three reaction wastes are difficult to treat. Therefore, how to artificially prepare 4-hydroxybenzyl alcohol with high yield and purity has become an urgent problem facing the medical researchers. Guided by the theory of microbial metabolic engineering, this study employed the genetic engineering technologies to introduce three genes ThiH, pchF and pchC into Escherichia coli for synthesizing 4-hydroxybenzyl alcohol with L-tyrosine. And the fermentation conditions of engineering strain for producing 4-hydroxybenzyl alcohol in shake flask were also discussed. The experimental results showed that under the conditions of 0.5 mmol·L~(-1) IPTG, 15 ℃ induction temperature, and 40 ℃ transformation temperature, M9 Y medium containing 200 mg·L~(-1) L-tyrosine could be transformed into(69±5)mg·L~(-1) 4-hydroxybenzyl alcohol, which has laid a foundation for producing 4-hydroxybenzyl alcohol economically and efficiently by further expanding the fermentation scale in the future.

中文翻译：

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L-酪氨酸在大肠杆菌中生物合成4-羟基苯甲醇的代谢工程研究[J].

4-羟基苯甲醇作为名贵中药天麻的重要活性成分，也是天麻素生物合成的主要前体，具有抗炎、抗肿瘤、抗脑缺血等多种药理活性。以4-羟基苯甲醇为主要成分的药品越来越受到青睐。目前，4-羟基苄醇主要通过天然提取和化学合成获得，但都存在一些缺点，限制了4-羟基苄醇的长期应用。野生和栽培的天麻资源有限。化学合成步骤多、时间长、反应条件苛刻。此外，产生的副产物量大，三种反应废物难以处理。所以，如何人工制备高收率、高纯度的4-羟基苯甲醇已成为医学研究人员亟待解决的问题。本研究以微生物代谢工程理论为指导，采用基因工程技术，将ThiH、pchF和pchC三个基因导入大肠杆菌，以L-酪氨酸合成4-羟基苯甲醇。并讨论了生产4-羟基苯甲醇的工程菌在摇瓶中的发酵条件。实验结果表明，在0.5 mmol·L~(-1) IPTG、15 ℃诱导温度和40 ℃转化温度条件下，含200 mg·L~(-1) L-酪氨酸的M9 Y培养基均能转化。成(69±5)mg·L~(-1) 4-羟基苯甲醇，