微生物合成5-羟基色氨酸的研究进展

Advances in microbial synthesis of 5-hydroxytryptophan

5-羟基色氨酸(5-hydroxytryptophan,5-HTP)是血清素和褪黑素生物合成的中间代谢物,可有效治疗多种疾病,如抑郁症、头痛、肥胖和失眠等。传统生产5-HTP的方法是植物提取或化学合成,然而,这些方法效率低,难以大规模生产,无法满足不断增长的市场需求。随着代谢工程和合成生物学的发展,利用微生物合成目标产物成为必然趋势。笔者综述了微生物合成5-HTP的研究进展,通过定向进化羟化酶以及引入辅酶因子合成与再生途径,实现了微生物合成5-HTP,再经代谢工程调控,通过平衡宿主细胞内代谢流提高5-HTP生产效率,为工业微生物有效合成5-HTP提供了理论基础和技术支持。

5-Hydroxytryptophan(5-HTP) is an intermediate metabolite in the biosynthetic pathway of serotonin and melatonin, which can effectively treat a variety of diseases, such as depression, headache, obesity and insomnia. Traditional methods to produce 5-HTP are natural extraction or chemical synthesis. However, these methods do not meet the growing needs of market due to inefficiency and inability to mass production. With the development of metabolic engineering and synthetic biology, it is an inevitable trend to use microorganisms to synthesize 5-HTP. A comprehensive review is made of the advances in microbial synthesis of 5-HTP.Microbial synthesis of 5-HTP is achieved through directed evolution of hydroxylase, the construction of coenzyme factor biosynthesis and regeneration pathways, and further metabolic engineering efforts are made to balance metabolic flow in the host cell to increase the production of 5-HTP. This review might provide a technical support for industrial biosynthesis of 5-HTP which is of guiding significance for large-scale industrial production of 5-HTP.