National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China; Key Laboratory of Industrial Biotechnology, Ministry of Education and School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China; Science Center for Future Foods, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, China.
School of Chemical Engineering, Zhengzhou University, Zhengzhou, China.
Enzyme Microb Technol. 2022 May;156:109991. doi: 10.1016/j.enzmictec.2022.109991. Epub 2022 Jan 6.
Flavonoids are a group of valuable compounds with a variety of health benefits. (2 S)-Naringenin is an important flavonoid skeleton, which can be tailored into almost all flavonoids. In this study, the Saccharomyces cerevisiae native precursor pathways were explored and higher-active CHSs from plants rich in flavonoids were screened. The results indicated that overexpressing the native precursor pathways is not an efficient approach to improving (2 S)-naringenin production in our chassis strain. On the other hand, by screening from plants rich in flavonoids, we obtained four CHSs with higher activities than the commonly used PhCHS. Among these CHSs, SjCHS1 increased the (2 S)-naringenin titer by 48.38% in shaking flasks. Finally, we combined the native precursor pathways optimization with the higher-active CHS that screened, and further increased the (2 S)-naringenin titer to 203.49 mg/L from glucose in shaking flasks. The results achieved in this study indicated that plants rich in flavonoids are good sources for higher-active CHS screening, and that the heterologous pathway and chassis precursor flux should be synergistically engineered to achieve higher production.
类黄酮是一组具有多种健康益处的有价值的化合物。（2S）-柚皮素是一种重要的黄酮类骨架，可以衍生出几乎所有的黄酮类化合物。在本研究中，探索了酿酒酵母天然前体途径，并筛选了富含类黄酮的植物中具有更高活性的 CHS。结果表明，过量表达天然前体途径不是提高底盘菌株中（2S）-柚皮素产量的有效方法。另一方面，通过从富含类黄酮的植物中筛选，我们获得了四种比常用的 PhCHS 具有更高活性的 CHS。在这些 CHS 中，SjCHS1 在摇瓶中使（2S）-柚皮素的产量提高了 48.38%。最后，我们将天然前体途径优化与筛选出的更高活性的 CHS 相结合，进一步将（2S）-柚皮素的产量从葡萄糖提高到 203.49mg/L 在摇瓶中。本研究的结果表明，富含类黄酮的植物是筛选更高活性 CHS 的良好来源，并且应该协同工程化异源途径和底盘前体通量以实现更高的产量。
