Artificial biosynthesis of phenylpropanoic acids in a tyrosine overproducing Escherichia coli strain.
Artificial biosynthesis of phenylpropanoic acids in a tyrosine overproducing Escherichia coli strain.
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DOI：
10.1186/1475-2859-11-153
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发表时间：
2012-12-03
影响因子：
6.4
通讯作者：
Hong YS
中科院分区：
文献类型：
--
作者：
Kang SY;Choi O;Lee JK;Hwang BY;Uhm TB;Hong YS
苯丙类代谢产物是由植物、真菌和细菌生物合成的一组极其多样化的天然产物。虽然这些化合物广泛用于人类保健和营养服务，但它们的可用性受到区域差异的限制，而且从植物中分离单一化合物往往很困难。合成生物学和代谢工程的最新进展使得在微生物中人工生产植物次生代谢物成为可能。我们开发了一种含有人工生物合成途径的大肠杆菌系统，该系统可以从简单的碳源中产生苯丙酸，如4-香豆酸，咖啡酸和阿魏酸。这些人工生物合成途径包含一个密码子优化的tal基因，可以提高4-香豆酸和阿魏酸的产量，但在低盐培养基中不能提高咖啡酸的产量。这些异源途径在具有过量生产酪氨酸的生物合成机制的大肠杆菌中扩展。最后，4-香豆酸、咖啡酸和阿魏酸在摇瓶中培养36小时，滴度分别达到974 mg/L、150 mg/L和196 mg/L。实现了4-香豆酸每升1克的规模生产。此外，咖啡酸和阿魏酸的最大滴度分别为150 mg/L和196 mg/L。苯基丙酸，如4-香豆酸、咖啡酸和阿魏酸，在制药和食品配料方面具有很大的应用潜力。这项工作为进一步提高产量奠定了基础，并开启了微生物合成更复杂的植物苯丙酸次生代谢物的可能性。
The phenylpropanoid metabolites are an extremely diverse group of natural products biosynthesized by plants, fungi, and bacteria. Although these compounds are widely used in human health care and nutrition services, their availability is limited by regional variations, and isolation of single compounds from plants is often difficult. Recent advances in synthetic biology and metabolic engineering have enabled artificial production of plant secondary metabolites in microorganisms. We develop an Escherichia coli system containing an artificial biosynthetic pathway that yields phenylpropanoic acids, such as 4-coumaric acid, caffeic acid, and ferulic acid, from simple carbon sources. These artificial biosynthetic pathways contained a codon-optimized tal gene that improved the productivity of 4-coumaric acid and ferulic acid, but not caffeic acid in a minimal salt medium. These heterologous pathways extended in E. coli that had biosynthesis machinery overproducing tyrosine. Finally, the titers of 4-coumaric acid, caffeic acid, and ferulic acid reached 974 mg/L, 150 mg/L, and 196 mg/L, respectively, in shake flasks after 36-hour cultivation. We achieved one gram per liter scale production of 4-coumaric acid. In addition, maximum titers of 150 mg/L of caffeic acid and 196 mg/L of ferulic acid were achieved. Phenylpropanoic acids, such as 4-coumaric acid, caffeic acid, and ferulic acid, have a great potential for pharmaceutical applications and food ingredients. This work forms a basis for further improvement in production and opens the possibility of microbial synthesis of more complex plant secondary metabolites derived from phenylpropanoic acids.
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