四氢嘧啶生物合成及其关键酶生化特性研究进展

Advances in ectoine biosynthesis and biochemical characteristics of key enzymes

摘要:

相容性溶质是微生物分泌的一类高水溶性有机渗透物，以适应高盐度和高渗透压等极端环境。四氢嘧啶(ectoine)作为一种重要的相容性溶质，对核酸、蛋白、生物膜以及细胞具有修复和保护作用，广泛应用于化妆品、生物制剂、酶工业和医疗等领域，每公斤市场售价约为1 000美元，全球每年需求量高达1.5万t。嗜盐菌是四氢嘧啶天然合成的微生物来源，但其需在高盐培养基中生长，工业化生产存在设备腐蚀以及成本高昂等问题。随着功能基因组学、系统生物学和合成生物学的快速发展，利用代谢工程等手段构建四氢嘧啶高产细胞工厂成为当前重要的研究方向，工程化大肠杆菌的四氢嘧啶最高产量已达131.8 g/L，产率为1.37 g/(L‧h)。本文主要围绕四氢嘧啶的合成途径、关键酶的生化特性以及四氢嘧啶生物合成等方面进行综述，以期阐明其研究现状并为四氢嘧啶的工业生产提供思路和方向。

关键词:四氢嘧啶;相容性溶质;生物合成;代谢工程

Abstract:

Compatible solutes are highly water-soluble organic osmolytes produced by microorganisms to adapt to extreme environments, such as high salinity and osmotic pressure. Among these, ectoine plays a crucial role in repairing and protecting nucleic acids, protein, biofilms, and cells. As a result, it has found widespread applications in cosmetics, biological agents, the enzyme industry, medicine, and other fields. Currently, the market value of ectoine is around US$ 1 000/kg, with a global demand reaching 15 000 tons per year. Although halophilic bacteria serve as the natural source of ectoine synthesis, its production in high-salinity media presents challenges such as equipment corrosion and high cost for industrial production. Advancements in functional genomics, systems biology, and synthetic biology have paved the way for the development of high-yielding cell factories through metabolic engineering, leading to significant progress. For example, engineered Escherichia coli achieved a maximum ectoine titer of 131.8 g/L, with a productivity of 1.37 g/(L‧h). This review aims to explore the biosynthetic pathway, biochemical characteristics of key enzymes, and the biosynthesis of ectoine, shedding light on current research status and offering insights for industrial-scale ectoine production.

Key words:ectoine;compatible solute;biosynthesis;metabolic engineering