School of Chemical and Biomedical Engineering, College of Engineering, Nanyang Technological University , 62 Nanyang Drive, Singapore 637459, Singapore.
J Agric Food Chem. 2017 Aug 9;65(31):6638-6646. doi: 10.1021/acs.jafc.7b02507. Epub 2017 Jul 28.
Flavonoids are an important class of plant polyphenols that possess a variety of health benefits. In this work, S. cerevisiae was metabolically engineered to produce the flavonoid naringenin, using tyrosine as the precursor. Our strategy to improve naringenin production comprised three modules. In module 1, we employed a modified GAL system to overexpress the genes of the naringenin biosynthesis pathway and investigated their synergistic action. In module 2, we simultaneously up-regulated acetyl-CoA production and down-regulated fatty acid biosynthesis in order to increase the precursor supply, malonyl-CoA. In module 3, we engineered the tyrosine biosynthetic pathway to eliminate the feedback inhibition of tyrosine and also down-regulated competing pathways. It was found that modules 1 and 3 played important roles in improving naringenin production. We succeeded in producing up to ∼90 mg/L of naringenin in our final strain, which is a 20-fold increase as compared to the parental strain.
类黄酮是一类重要的植物多酚，具有多种健康益处。在这项工作中，我们通过代谢工程改造酿酒酵母，以酪氨酸为前体生产类黄酮柚皮素。我们提高柚皮素产量的策略包括三个模块。在模块 1 中，我们采用改良的 GAL 系统过表达柚皮素生物合成途径的基因，并研究它们的协同作用。在模块 2 中，我们同时上调乙酰辅酶 A 的产生并下调脂肪酸的生物合成，以增加前体供应，丙二酰辅酶 A。在模块 3 中，我们对酪氨酸生物合成途径进行了工程改造，以消除酪氨酸的反馈抑制，同时下调竞争途径。结果表明，模块 1 和模块 3 对提高柚皮素的产量起着重要作用。我们成功地在最终菌株中生产出了高达 90mg/L 的柚皮素，比原始菌株提高了 20 倍。
