微生物合成L-脯氨酸和反式-4-羟基-L-脯氨酸的研究进展

Advances on microbial synthesis of l-proline and trans-4-hydroxy-l-proline

摘要:

l-脯氨酸(l-proline,l-Pro)是构成生物体蛋白质20种氨基酸中唯一的一种亚氨基酸，其羟基化后的产物主要是反式-4-羟基-L-脯氨酸(trans-4-hydroxy-l-proline,T-4-Hyp)，两者均具有独特的生物活性，在生物医药和食品美容方面发挥着不可替代的作用。随着对l-Pro和T-4-Hyp功能的深度挖掘，这两者的需求与日俱增，传统生物提取和化学合成的方法已无法满足当今社会“绿色、环保、高效”的需求。近年来，合成生物学迅猛发展，通过深入解析l-Pro和T-4-Hyp的合成途径，构建了微生物细胞工厂用于规模化生产，为绿色高效生产l-Pro和T-4-Hyp开启了新的篇章。本文综述了l-Pro和T-4-Hyp的应用与生产方法、微生物合成l-Pro和T-4-Hyp的代谢途径以及微生物生产l-Pro和T-4-Hyp的改造策略与研究进展，旨在为l-Pro和T-4-Hyp的“绿色生物制造”提供理论基础，促进其工业化生产。

关键词:l-脯氨酸;反式-4-羟基-l-脯氨酸;生物合成;代谢工程;微生物生产

Abstract:

l-proline (l-Pro) is the only imino acid among the 20 amino acids that constitute biological proteins, and its main hydroxylated product is trans-4-hydroxy-l-proline (T-4-Hyp). Both of them have unique biological activities and play important roles in biomedicine, food and beauty industry. With the in-depth exploration of the functions of l-Pro and T-4-Hyp, the demand for them is gradually increasing. Traditional methods of biological extraction and chemical synthesis are unable to meet the demand of “green, environmental protection and high efficiency”. In recent years, synthetic biology has developed rapidly. Through the intensive analysis of the synthetic pathways of l-Pro and T-4-Hyp, microbial cell factories were constructed for large-scale production, which opened a new chapter for the green and efficient production of l-Pro and T-4-Hyp. This paper reviews the application and production methods of l-Pro and T-4-Hyp, the metabolic pathways for microbial synthesis of l-Pro and T-4-Hyp, and the engineering strategies and advances on microbial production of l-Pro and T-4-Hyp, aiming to provide a theoretical basis for the “green bio-manufacturing” of l-Pro and T-4-Hyp and promote their industrial production.

Key words:l-proline;trans-4-hydroxy-l-proline;biosynthesis;metabolic engineering;microbial production