Enhanced production of 5-hydroxytryptophan through the regulation of L-tryptophan biosynthetic pathway

Xu, Dan; Fang, Mengjun; Wang, Haijiao; Huang, Lei; Xu, Qinyang; Xu, Zhinan

doi:10.1007/s00253-020-10371-y

Cited by 28 publications

(23 citation statements)

References 22 publications

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“…To regulate the production of 5-HTP, they also regulated the copy number of the L-TPH coding gene plasmid. After these optimization steps, the amount of 5-HTP of shake flask fermentation increased to 1.61 g/ml, which was 24% higher than that of the original strain (Table 1) (Xu et al, 2020).…”

Section: Optimization Of Trp Supplymentioning

confidence: 92%

Advances in the Microbial Synthesis of 5-Hydroxytryptophan

Liu

Zhang

2021

Front. Bioeng. Biotechnol.

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5-Hydroxytryptophan (5-HTP) plays an important role in the regulation of emotion, behavior, sleep, pain, body temperature, and other physiological functions. It is used in the treatment of depression, insomnia, migraine, and other diseases. Due to a lack of effective biosynthesis methods, 5-HTP is mainly obtained by natural extraction, which has been unable to meet the needs of the market. Through the directed evolution of enzymes and the introduction of substrate supply pathways, 5-HTP biosynthesis and yield increase have been realized. This review provides examples that illustrate the production mode of 5-HTP and the latest progress in microbial synthesis.

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Section: Optimization Of Trp Supplymentioning

confidence: 92%

Advances in the Microbial Synthesis of 5-Hydroxytryptophan

Liu

Zhang

2021

Front. Bioeng. Biotechnol.

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“…Para a atividade aguda, doses orais únicas de 5 -HTP (1,5, 5 e 20 mg/kg) foram dados aos ratos 1,5 horas antes do teste da carragenina. Para a atividade crônica, as mesmas doses orais foram dadas cada dia durante duas semanas antes do teste da carragenina no 14º dia.…”

Section: Métodosunclassified

“…Certain factors like stress and insulin resistance affect this step, leading to the decrease of serotonin production [1][2][3]. Brain serotonin level is mostly dependent on 5-HTP which, in contrast to serotonin, easily crosses the blood-brain barrier and is almost fully absorbed from an oral dose [4,5]. Therefore, 5-HTP has become a frequently used supplement for the treatment of anxiety and depression for many years and its efficacy in these illnesses has been shown by several clinical trials [6,7].…”

Section: Introductionmentioning

confidence: 99%

The effects of 5-hydroxytryptophan on carrageenan-induced mouse paw oedemas

2021

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Objective 5-Hydroxytryptophan is the precursor compound of serotonin biosynthesis. The oral absorption of 5-Hydroxytryptophan is close to 100% and, unlike serotonin, it crosses the blood-brain barrier freely. 5-Hydroxytryptophan has been used as a food supplement for many years to treat anxiety and depression. Recent studies have shown that 5-Hydroxytryptophan suppresses the pro-inflammatory mediators and is effective in some inflammatory diseases, such as arthritis and allergic asthma. However, the role of 5-Hydroxytryptophan supplements on acute peripheral inflammation has not been investigated yet. In this study, the in vivo anti-inflammatory activity of 5-Hydroxytryptophan was evaluated with a carrageenan-induced paw oedema test in mice. Methods For the investigation of the acute antiinflammatory activity, single oral doses of 5-Hydroxytryptophan (1.5, 5 and 20mg/kg) were given to mice 1.5 hours prior to the carrageenan test. For chronic activity, the same oral doses were administered daily for two weeks prior to the carrageenan test on the 14th day. To induce inflammation, 0.01mL of 2% carrageenan was injected into the paws of mice. Results Supplementation with 5-Hydroxytryptophan significantly reduced inflammation in a dose-independent manner which was irrespective of the duration of exposure (per cent inhibition in acute experiments was 35.4%, 20.9%, 24.0%, and per cent inhibition in chronic experiments was 29.5%, 35.3%, 40.8% for the doses of 1.5, 5, and 20mg/kg, respectively). Conclusion Our findings demonstrate for the first time that 5-HTP supplements have the potential of suppressing the measures of acute peripheral inflammation. It is suggested that, apart from several diseases where serotonin is believed to play an important role, including depression, patients with inflammatory conditions may also benefit from 5-HTP.

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“…Previous studies have shown that 5-HT can be produced from L-trp in the nervous system of human and animals via two enzymatic steps: L-trp is hydroxylated to 5-HTP by pterin-dependent tryptophan hydroxylase (TPH), then converted to 5-HT by pyridoxal 5phosphatemonohydrate (PLP)-dependent tryptophan decarboxylase (TDC) [8]. However, the protocol has several issues, including the problems that TPH possesses poor stability and the expensive cofactor, pterin, is required [5,9]. Aromatic amino acid decarboxylases (AAADs) play important roles in the key step of 5-HTP conversion to 5-HT.…”

Section: Introductionmentioning

confidence: 99%

“…L-tryptophan (L-trp) is an essential amino acid, and its derivatives, such as L-5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), N-Acetyl-5-hydroxytryptamine and melatonin, have gained increasing attention due to their direct health and medical bene ts, and their production of other valuable molecules as key biosynthetic precursors [1][2][3][4]. Among these, 5-HT is a major neurotransmitter that is naturally present in animals and plants [5]. Similar to the catecholamines, dopamine, epinephrine, and norepinephrine, 5-HT modulates the activity of the nervous system and plays a signi cant role in the coordination of movement and the regulation of mood.…”

Section: Introductionmentioning

confidence: 99%

Construction of Cell Factory Capable of Efficiently Converting L-tryptophan Into 5-hydroxytryptamine

Wang

Chen

et al. 2021

Preprint

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Background: L-Tryptophan (L-trp) derivatives such as 5-hydroxytryptophan (5-HTP) and 5-hydroxytryptamine (5-HT), N-Acetyl-5-hydroxytryptamine and melatonin are important molecules with pharmaceutical interest. Among, 5-HT is an inhibitory neurotransmitter with proven benefits for treating the symptoms of depression. At present, 5-HT depends on plant extraction and chemical synthesis, which limits its mass production and causes environmental problems. Therefore, it is necessary to develop an efficient, green and sustainable biosynthesis method to produce 5-HT.Results: Here we propose a one-pot production of 5-HT from L-trp via two enzyme cascades for the first time. First, a chassis cell that can convert L-trp into 5-HTP was constructed by heterologous expression of tryptophan hydroxylase from Schistosoma mansoni (SmTPH) and an artificial endogenous BH4 module. Then, dopa decarboxylase from Harminia axyridis (HaDDC), which can specifically catalyse 5-HTP to 5-HT, was used for 5-HT production. The cell factory, E. coli BL21(DE3)△tnaA/BH4/HaDDC-SmTPH, which contains SmTPH and HaDDC, was constructed for 5-HT synthesis. The highest concentration of 5-HT reached 414.5 ± 1.6 mg/L (with conversion rate of 43 mol%) at the optimal conditions (induced temperature, 25℃; IPTG concentration, 0.5 mM; catalysis temperature, 30℃; catalysis time, 72 h). Conclusions: This protocol provided an efficient one-pot method for converting L-trp into 5-HT production, which opens up possibilities for the practical biosynthesis of natural 5-HT at an industrial scale.

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Enhanced production of 5-hydroxytryptophan through the regulation of L-tryptophan biosynthetic pathway

Cited by 28 publications

References 22 publications

Advances in the Microbial Synthesis of 5-Hydroxytryptophan

Advances in the Microbial Synthesis of 5-Hydroxytryptophan

The effects of 5-hydroxytryptophan on carrageenan-induced mouse paw oedemas

Construction of Cell Factory Capable of Efficiently Converting L-tryptophan Into 5-hydroxytryptamine

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