Metabolic engineering of Escherichia coli for production of salvianic acid A via an artificial biosynthetic pathway.
Metabolic engineering of Escherichia coli for production of salvianic acid A via an artificial biosynthetic pathway.
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DOI：
10.1016/j.ymben.2013.06.001
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发表时间：
2013-09
影响因子：
8.4
通讯作者：
Yuan-Feng Yao;Chang-Song Wang;Jianjun Qiao;Guang-Rong Zhao
中科院分区：
文献类型：
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作者：
Yuan-Feng Yao;Chang-Song Wang;Jianjun Qiao;Guang-Rong Zhao
丹参酸A是丹参L-酪氨酸生物合成途径的重要衍生物，具有抗氧化活性和治疗心血管疾病的作用。传统的方法是从植物根中提取或通过化学方法合成丹参素A，但效率较低。在此，我们开发了一个前所未有的人工生物合成途径的丹酚酸A inE。大肠杆菌，使其生产从葡萄糖直接。在该途径中，4-羟基苯丙酮酸通过D-乳酸脱氢酶（编码戊糖乳杆菌的byd-ldh）和羟化酶复合物（编码E.大肠杆菌）。此外，我们通过模块化工程方法和删除参与调控和竞争途径的基因来优化该途径。代谢工程E.该菌株产丹参素A的能力为7.1g/L，产率为0.47mol/mol葡萄糖。
Salvianic acid A, a valuable derivative from L-tyrosine biosynthetic pathway of the herbal plant Salvia miltiorrhiza, is well known for its antioxidant activities and efficacious therapeutic potential on cardiovascular diseases. Salvianic acid A was traditionally isolated from plant root or synthesized by chemical methods, both of which had low efficiency. Herein, we developed an unprecedented artificial biosynthetic pathway of salvianic acid A inE. coli, enabling its production from glucose directly. In this pathway, 4-hydroxyphenylpyruvate was converted to salvianic acid A via D-lactate dehydrogenase (encoding byd-ldhfrom Lactobacillus pentosus) and hydroxylase complex (encoding byhpaBCfromE. coli). Furthermore, we optimized the pathway by a modular engineering approach and deleting genes involved in the regulatory and competing pathways. The metabolically engineeredE. colistrain achieved high productivity of salvianic acid A (7.1 g/L) with a yield of 0.47 mol/mol glucose.