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1.厦门大学生命科学学院,细胞应激生物学国家重点实验室,福建 厦门 361102
2.厦门大学生物医药前沿交叉学院,福建 厦门 361102
lizhizhen@stu.xmu.edu.cn
Received:13 July 2026,
Revised:2026-09-29,
Online First:09 October 2026,
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张阳, 李志臻, 高馨语, 陈浩锋, 袁吉锋. 微生物法合成维生素E研究进展[J]. 合成生物学, 2026, 7. DOI: 10.12211/2096-8280.2026-061
ZHANG Yang, LI Zhizhen, GAO Xinyu, CHEN Haofeng, YUAN Jifeng. Research Progress on Microbial Synthesis of Vitamin E[J]. Synthetic Biology Journal, 2026, 7. DOI: 10.12211/2096-8280.2026-061
维生素E是一类脂溶性抗氧化剂,兼具重要的生理功能与庞大的市场需求。传统化学全合成法所得产物生物活性低、环境不友好;天然植物油提取法则受限于原料供应与成本,难以满足可持续发展需求。微生物发酵法凭借原料可再生、过程绿色、产物为单一天然构型等优势,成为维生素E绿色制造的前沿方向。本文重点阐述了大肠杆菌、酵母及紫色非硫光合细菌等工程化底盘细胞在维生素E异源合成中的研究进展,分析了前体供应强化、关键酶优化、膜工程与转运工程、辅因子优化及发酵工艺改进等策略。近年来,合成生物学的发展为微生物异源合成维生素E提供了工程化改造的新思路。通过酶工程改造、转运蛋白筛选及原位萃取等技术突破,结合传统的代谢工程改造,维生素E产量已从微克每升级别提升至克级每升水平,其中球形红细菌中生育酚产量达到3.51 g/L,创下最高纪录。最后,本文从新型酶资源挖掘、辅因子全局优化、产物耐受性改造、发酵—分离耦合、人工智能驱动的细胞工厂设计等方面展望了未来的研究方向,以期为维生素E及其他脂溶性天然产物的微生物合成提供参考。
Vitamin E is a group of essential lipid-soluble vitamins with antioxidant
anti-aging
anti-tumor and other physiological activities. It plays critical roles in maintaining normal human physiological functions
preventing cardiovascular diseases
and treating Alzheimer's disease. As living standards improve globally
vitamin E is widely utilized as a nutritional supplement and antioxidant in feed
pharmaceutical
food and cosmetic industries
generating enormous market demand. At present
more than 80% of vitamin E worldwide is manufactured via total chemical synthesis. However
traditional chemical synthesis relies on petroleum-based raw materials
causes severe environmental pollution
and fails to meet the market demand for vitamin E monomers with specific stereoconfigurations. Extraction from natural vegetable oils is constrained by raw material supply and high production costs
and cannot satisfy sustainable development requirements. By comparison
microbial fermentation has emerged as a sustainable alternative for biomanufacturing of vitamin E
owing to advantages such as renewable feedstocks
eco-friendly manufacturing processes
and the production of natural single stereoisomers. This review systematically summarizes research advances in the heterologous biosynthesis of vitamin E using e
ngineered chassis cells including
Escherichia coli
yeast and purple non-sulfur photosynthetic bacteria. Engineering strategies—including enhancement of precursor supply
optimization of key enzymes
membrane and transport engineering
cofactor tuning
as well as fermentation process upgrading—are critically analyzed. In recent years
advances in synthetic biology have offered innovative strategies for engineering microbial hosts to heterologously synthesize vitamin E. Combined with traditional metabolic engineering
technological breakthroughs such as enzyme engineering
transporter screening
and in situ extraction have drastically raised vitamin E titers from micrograms per liter to grams per liter levels. Notably
the record-high tocopherol titer of 3.51 g/L has been achieved in engineered
Rhodobacter sphaeroides
. Finally
future research perspectives are proposed from five aspects: exploration of novel enzyme resources
global cofactor optimization
strain engineering for improved product tolerance
integrated fermentation-separation systems
and artificial intelligence-assisted design of microbial cell factories. This work aims to provide theoretical and technical references for the microbial synthesis of vitamin E and other lipid-soluble natural products.
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