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Enhanced production of 5-hydroxytryptophan through the regulation of L-tryptophan biosynthetic pathway.
Applied Microbiology and Biotechnology ( IF 3.9 ) Pub Date : 2020-01-31 , DOI: 10.1007/s00253-020-10371-y
Da Xu 1 , Mengjun Fang 2, 3 , Haijiao Wang 2, 3 , Lei Huang 2, 3 , Qinyang Xu 1 , Zhinan Xu 2, 3
Affiliation  

5-Hydroxytryptophan (5-HTP) is the precursor of the neurotransmitter serotonin and has been used for the treatment of various diseases such as depression, insomnia, chronic headaches, and binge eating associated obesity. The production of 5-HTP had been achieved in our previous report, by the development of a recombinant strain containing two plasmids for biosynthesis of L-tryptophan (L-trp) and subsequent hydroxylation. In this study, the L-trp biosynthetic pathway was further integrated into the E. coli genome, and the promoter strength of 3-deoxy-7-phosphoheptulonate synthase, which catalyzes the first step of L-trp biosynthesis, was engineered to increase the production of L-trp. Hence, the 5-HTP production could be manipulated by the regulation of copy number of L-trp hydroxylation plasmid. Finally, the 5-HTP production was increased to 1.61 g/L in the shaking flasks, which was 24% improvement comparing to the original producing strain, while the content of residual L-trp was successfully reduced from 1.66 to 0.2 g/L, which is beneficial for the downstream separation and purification. Our work shall promote feasible progresses for the industrial production of 5-HTP.

中文翻译:

通过调节L-色氨酸的生物合成途径提高了5-羟色氨酸的产量。

5-羟色氨酸(5-HTP)是神经递质血清素的前体,已用于治疗各种疾病,例如抑郁症,失眠,慢性头痛和暴饮暴食引起的肥胖。在我们以前的报告中,通过开发包含两个用于L-色氨酸(L-trp)生物合成和随后的羟基化反应的质粒的重组菌株,已经实现了5-HTP的生产。在这项研究中,L-trp生物合成途径被进一步整合到大肠杆菌基因组中,并且设计了催化L-trp生物合成第一步的3-deoxy-7-phosphoheptulonate合酶的启动子强度,从而增加了L-trp生物合成途径。 L-trp的生产。因此,可以通过调节L-trp羟基化质粒的拷贝数来操纵5-HTP的产生。最后,将5-HTP产量提高到1。摇瓶中61 g / L,与原始生产菌株相比提高了24%,而残留L-trp的含量成功地从1.66降低至0.2 g / L,这对下游的分离和纯化是有利的。我们的工作将促进5-HTP工业生产的可行进展。
更新日期:2020-02-27
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