Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China.
J Biotechnol. 2013 Sep 20;167(4):404-11. doi: 10.1016/j.jbiotec.2013.07.030. Epub 2013 Jul 31.
Microbial fermentations and bioconversion promise to revolutionize the conventional extraction of resveratrol from natural plant sources. However, the development of efficient and feasible microbial processes remains challenging. Current fermentation strategies often require supplementation of expensive phenylpropanoic precursors and two separate fermentation protocols, which are significantly more difficult and expensive to undertake when migrating to large-scale fermentation processes. In this study, an Escherichia coli fermentation system, consisting of tyrosine ammonia lyase (TAL), 4-coumarate:CoA ligase (4CL), stilbene synthase (STS), malonate synthetase, and malonate carrier protein, was developed to produce resveratrol from L-tyrosine. Multivariate modular metabolic engineering, which redefined the overall pathway as a collection of distinct modules, was employed to assess and alleviate pathway bottlenecks. Using this strategy, the optimum strain was capable of producing 35.02 mg/L of resveratrol from L-tyrosine in a single medium. The strategy described here paves the way to the development of a simple and economical process for microbial production of resveratrol and other similar stilbene chemicals.
微生物发酵和生物转化有望彻底改变从天然植物资源中提取白藜芦醇的传统方法。然而，开发高效可行的微生物工艺仍然具有挑战性。目前的发酵策略通常需要昂贵的苯丙酸前体的补充，以及两个独立的发酵方案，当迁移到大规模发酵过程时，这两个方案更加困难和昂贵。在这项研究中，开发了一种大肠杆菌发酵系统，该系统由酪氨酸氨裂解酶（TAL）、4-香豆酸：CoA 连接酶（4CL）、芪合酶（STS）、丙二酸合成酶和丙二酸载体蛋白组成，可从 L-酪氨酸生产白藜芦醇。采用多变量模块化代谢工程，将整个途径重新定义为一系列不同的模块，以评估和缓解途径瓶颈。使用该策略，最佳菌株能够在单一培养基中从 L-酪氨酸生产 35.02 毫克/升的白藜芦醇。这里描述的策略为微生物生产白藜芦醇和其他类似的芪类化学品开辟了一条简单经济的工艺开发之路。
