Li Yuanzi, Li Jiaxin, Zhang Miao, Liao Yonghong, Wang Fenghuan, Qiao Mingqiang
School of Light Industry Science and Engineering, Beijing Technology and Business University (BTBU), Beijing, China.
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, China.
Front Microbiol. 2025 Apr 29;16:1570406. doi: 10.3389/fmicb.2025.1570406. eCollection 2025.
Caffeic acid, a plant-derived phenolic compound, has attracted much attention in the fields of medicines and cosmetics due to its remarkable physiological activities including antioxidant, anti-inflammation, antibacteria, antivirus and hemostasis. However, traditional plant extraction and chemical synthesis methods exist some problems such as high production costs, low extraction efficiency and environmental pollution. In recent years, the construction of microbial cell factories for the biosynthesis of caffeic acid has attracted much attention due to its potential to offer an efficient and environmentally-friendly alternative for caffeic acid production. This review introduces the caffeic acid biosynthesis pathway first, after which the characteristics of microbial hosts for caffeic acid production are analyzed. Then, the main strategies for caffeic acid production in microbial hosts, including selection and optimization of heterologous enzymes, enhancement of the metabolic flux to caffeic acid, supply and recycling of cofactor, and optimization of the production process, are summarized and discussed. Finally, the future prospects and perspectives of microbial caffeic acid production are discussed. Recent breakthroughs have achieved caffeic acid titers of up to 6.17 g/L, demonstrating the potential of microbial biosynthesis. Future research can focus on the enhancement of metabolic flux to caffeic acid biosynthesis pathway, the development of robust microbial hosts with improved tolerance to caffeic acid and its precursors, and the establishment of cost-effective industrial production processes.
咖啡酸是一种植物源酚类化合物，因其具有抗氧化、抗炎、抗菌、抗病毒和止血等显著生理活性，在医药和化妆品领域备受关注。然而，传统的植物提取和化学合成方法存在生产成本高、提取效率低和环境污染等问题。近年来，构建用于生物合成咖啡酸的微生物细胞工厂因其有可能为咖啡酸生产提供一种高效且环保的替代方法而备受关注。本文首先介绍了咖啡酸的生物合成途径，然后分析了用于生产咖啡酸的微生物宿主的特性。接着，总结并讨论了在微生物宿主中生产咖啡酸的主要策略，包括异源酶的选择和优化、增强通向咖啡酸的代谢通量、辅因子的供应和循环以及生产工艺的优化。最后，探讨了微生物生产咖啡酸的未来前景。最近的突破已实现高达6.17 g/L的咖啡酸滴度，证明了微生物生物合成的潜力。未来的研究可以集中在增强通向咖啡酸生物合成途径的代谢通量、开发对咖啡酸及其前体具有更高耐受性的强大微生物宿主，以及建立具有成本效益的工业生产工艺。
