Xiang Jinbo, Liu Mengsu, Wang Xinglong, Yue Mingyu, Qin Zhijie, Zhou Jingwen
Engineering Research Center of Ministry of Education on Food Synthetic Biotechnology, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu, 214122, China.
Science Center for Future Foods, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
Synth Syst Biotechnol. 2025 Feb 20;10(3):719-727. doi: 10.1016/j.synbio.2025.02.011. eCollection 2025 Sep.
δ-Tocotrienol, an isomer of vitamin E with anti-inflammatory, neuroprotective and anti-coronary arteriosclerosis properties, is widely used in health care, medicine and other fields. Microbial synthesis of δ-tocotrienol offers significant advantages over plant extraction and chemical synthesis methods, including increased efficiency, cost-effectiveness and environmental sustainability. However, limited precursor availability and low catalytic efficiency of key enzymes remain major bottlenecks in the biosynthesis of δ-tocotrienol. In this study, we assembled the complete δ-tocotrienol biosynthetic pathway in and enhanced the precursor supply, resulting in a titre of 102.8 mg/L. The catalytic efficiency of the rate-limiting steps in the pathway was then enhanced through various strategies, including fusion expression of key enzymes homogentisate phytyltransferaseand and tocopherol cyclase, semi-rational design of SyHPT and multi-copy integration of pathway genes. The final a δ-tocotrienol titre in a 5 L bioreactor was 466.8 mg/L following fed-batchfermentation. This study represents the first successful biosynthesis of δ-tocotrienol in , providing valuable insights into the synthesis of vitamin E-related compounds.
δ-生育三烯酚是维生素E的一种异构体，具有抗炎、神经保护和抗冠状动脉粥样硬化特性，广泛应用于医疗保健、医药等领域。与植物提取和化学合成方法相比，微生物合成δ-生育三烯酚具有显著优势，包括提高效率、成本效益和环境可持续性。然而，前体可用性有限和关键酶的催化效率低仍然是δ-生育三烯酚生物合成的主要瓶颈。在本研究中，我们在[具体生物]中组装了完整的δ-生育三烯酚生物合成途径，并增强了前体供应，产量达到102.8 mg/L。然后通过各种策略提高了该途径中限速步骤的催化效率，包括关键酶尿黑酸植基转移酶和生育酚环化酶的融合表达、尿黑酸植基转移酶的半理性设计以及途径基因的多拷贝整合。补料分批发酵后，5 L生物反应器中δ-生育三烯酚的最终产量为466.8 mg/L。本研究代表了首次在[具体生物]中成功生物合成δ-生育三烯酚，为维生素E相关化合物的合成提供了有价值的见解。
