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L-5-Hydroxytryptophan Sale

(Synonyms: 5-羟基色氨酸; L-5-HTP; Oxitriptan) 目录号 : GC36416

An intermediate in serotonin biosynthesis

L-5-Hydroxytryptophan Chemical Structure

Cas No.:4350-09-8

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10mM (in 1mL DMSO)
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产品描述

5-hydroxy-L-Tryptophan (5-HTP) is an intermediate in the biosynthesis of serotonin from tryptophan.1 When injected systemically in animals, 5-HTP is converted to serotonin and has both peripheral and central nervous system effects.2,3,4 In ex vivo studies, 5-HTP can be metabolized to melatonin with circadian rhythmicity, using serotonin as an intermediate.5 5-HTP can also be synthesized by gut microbiota and acts as an activator of the aryl hydrocarbon receptor.6

1.Martinez, A., Knappskog, P.M., and Haavik, J.A structural approach into human tryptophan hydroxylase and its implications for the regulation of serotonin biosyntheisCurr. Med. Chem.8(9)1077-1091(2001) 2.Haberzettl, R., Fink, H., and Bert, B.The murine serotonin syndrome - evaluation of responses to 5-HT-enhancing drugs in NMRI miceBehav. Brain Res.277204-210(2015) 3.Laporta, J., Moore, S.A.E., Weaver, S.R., et al.Increasing serotonin concentrations alter calcium and energy metabolism in dairy cowsJ. Endocrinol.226(1)43-55(2015) 4.Schmid, C.L., and Bohn, L.M.Serotonin, but not N-methyltryptamines, activates the serotonin 2A receptor via a β-arrestin2/Src/Akt signaling complex in vivoJ. Neurosci.30(40)13513-13524(2010) 5.Cahill, G.M., and Besharse, J.C.Circadian regulation of melatonin in the retina of Xenopus laevis: imitation by serotonin availabilityJ. Neurochem.54(2)716-719(1990) 6.Sridharan, G.V., Choi, K., Klemashevich, C., et al.Prediction and quantification of bioactive microbiota metabolites in the mouse gutNat. Commun.55492(2014)

Chemical Properties

Cas No. 4350-09-8 SDF
别名 5-羟基色氨酸; L-5-HTP; Oxitriptan
Canonical SMILES N[C@@H](CC1=CNC2=CC=C(O)C=C12)C(O)=O
分子式 C11H12N2O3 分子量 220.22
溶解度 DMSO: 100 mg/mL (454.09 mM) 储存条件 Store at -20°C
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Research Update

5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology

Int J Mol Sci 2020 Dec 26;22(1):181.PMID:33375373DOI:10.3390/ijms22010181.

L-5-Hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed to melatonin (N-acetyl-5-methoxytryptamine). 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis. In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials. The physiological role of 5-HTP in the treatment of depression, anxiety, panic, sleep disorders, obesity, myoclonus and serotonin syndrome are also discussed. 5-HTP toxicity and the occurrence of toxic impurities present in tryptophan and 5-HTP preparations are also discussed.

L-5-Hydroxytryptophan promotes antitumor immunity by inhibiting PD-L1 inducible expression

J Immunother Cancer 2022 Jun;10(6):e003957.PMID:35728870DOI:10.1136/jitc-2021-003957.

Background: The repression or downregulation of programmed death-ligand 1 (PD-L1) can release its inhibition of T cells and activate antitumor immune responses. Although PD-1 and PD-L1 antibodies are promising treatments for diverse tumor types, their inherent disadvantages and immune-related adverse events remain significant issues. The development of small molecule inhibitors targeting the interaction surface of PD-1 and PD-L1 has been reviving, yet many challenges remain. To address these issues, we aimed to find small molecules with durable efficacy and favorable biosafety that alter PD-L1 surface expression and can be developed into a promising alternative and complementary therapy for existing anti-PD-1/PD-L1 therapies. Methods: Cell-based screen of 200 metabolic molecules using a high-throughput flow cytometry assay of PD-L1 surface expression was conducted, and L-5-Hydroxytryptophan (L-5-HTP) was found to suppress PD-L1 expression induced by interferon gamma (IFN-γ). Inhibition of PD-L1 induction and antitumor effect of L-5-HTP were evaluated in two syngeneic mouse tumor models. Flow cytometry was performed to investigate the change in the tumor microenvironment caused by L-5-HTP treatment. Results: We discovered that L-5-HTP suppressed IFN-γ-induced PD-L1 expression in tumor cells transcriptionally, and this effect was directly due to itself. Mechanistically, L-5-HTP inhibited IFN-γ-induced expression of RTK ligands and thus suppressed phosphorylation-mediated activation of RTK receptors and the downstream MEK/ERK/c-JUN signaling cascade, leading to decreased PD-L1 induction. In syngeneic mouse tumor models, treatment with 100 mg/kg L-5-HTP (intraperitoneal) inhibited PD-L1 expression and exhibited antitumor effect. L-5-HTP upregulated the ratio of granzyme B+ CD8+ activated cytotoxic T cells. An intact immune system and PD-L1 expression was critical for L-5-HTP to exert its antitumor effects. Furthermore, L-5-HTP acted synergistically with PD-1 antibody to improve anticancer effect. Conclusion: Our study illustrated L-5-HTP's inhibitory effect on PD-L1 induction stimulated by IFN-γ in tumor cells and also provided insight into repurposing L-5-HTP for use in tumor immunotherapy.

Metabolic engineering of Escherichia coli for efficient production of L-5-Hydroxytryptophan from glucose

Microb Cell Fact 2022 Sep 24;21(1):198.PMID:36153615DOI:10.1186/s12934-022-01920-3.

Background: 5-hydroxytryptophan (5-HTP), the direct biosynthetic precursor of the neurotransmitter 5-hydroxytryptamine, has been shown to have unique efficacy in the treatment of a variety of disorders, including depression, insomnia, and chronic headaches, and is one of the most commercially valuable amino acid derivatives. However, microbial fermentation for 5-HTP production continues to face many challenges, including low titer/yield and the presence of the intermediate L-tryptophan (L-Trp), owing to the complexity and low activity of heterologous expression in prokaryotes. Therefore, there is a need to construct an efficient microbial cell factory for 5-HTP production. Results: We describe the systematic modular engineering of wild-type Escherichia coli for the efficient fermentation of 5-HTP from glucose. First, a xylose-induced T7 RNA polymerase-PT7 promoter system was constructed to ensure the efficient expression of each key heterologous pathway in E. coli. Next, a new tryptophan hydroxylase mutant was used to construct an efficient tryptophan hydroxylation module, and the cofactor tetrahydrobiopterin synthesis and regeneration pathway was expressed in combination. The L-Trp synthesis module was constructed by modifying the key metabolic nodes of tryptophan biosynthesis, and the heterologous synthesis of 5-HTP was achieved. Finally, the NAD(P)H regeneration module was constructed by the moderate expression of the heterologous GDHesi pathway, which successfully reduced the surplus of the intermediate L-Trp. The final engineered strain HTP11 was able to produce 8.58 g/L 5-HTP in a 5-L bioreactor with a yield of 0.095 g/g glucose and a maximum real-time productivity of 0.48 g/L/h, the highest values reported by microbial fermentation. Conclusion: In this study, we demonstrate the successful design of a cell factory for high-level 5-HTP production, combined with simple processes that have potential for use in industrial applications in the future. Thus, this study provides a reference for the production of high-value amino acid derivatives using a systematic modular engineering strategy and a basis for an efficient engineered strain development of 5-HTP high-value derivatives.

Directed Evolution Improves the Enzymatic Synthesis of L-5-Hydroxytryptophan by an Engineered Tryptophan Synthase

Appl Biochem Biotechnol 2021 Oct;193(10):3407-3417.PMID:34097254DOI:10.1007/s12010-021-03589-7.

L-5-Hydroxytryptophan is an important amino acid that is widely used in food and medicine. In this study, L-5-Hydroxytryptophan was synthesized by a modified tryptophan synthase. A direct evolution strategy was applied to engineer tryptophan synthase from Escherichia coli to improve the efficiency of L-5-Hydroxytryptophan synthesis. Tryptophan synthase was modified by error-prone PCR. A high-activity mutant enzyme (V231A/K382G) was obtained by a high-throughput screening method. The activity of mutant enzyme (V231A/K382G) is 3.79 times higher than that of its parent, and kcat/Km of the mutant enzyme (V231A/K382G) is 4.36 mM-1∙s-1. The mutant enzyme (V231A/K382G) reaction conditions for the production of L-5-Hydroxytryptophan were 100 mmol/L L-serine at pH 8.5 and 35°C for 15 h, reaching a yield of L-5-Hydroxytryptophan of 86.7%. Directed evolution is an effective strategy to increase the activity of tryptophan synthase.

5-Hydroxytryptophan, but not L-tryptophan, alters sleep and brain temperature in rats

Neuroscience 2000;95(2):445-52.PMID:10658624DOI:10.1016/s0306-4522(99)00435-2.

The precise role of serotonin (5-hydroxytryptamine) in the regulation of sleep is not fully understood. To further clarify this role for 5-hydroxytryptamine, the 5-hydroxytryptamine precursors L-tryptophan (40 and 80 mg/kg) and L-5-Hydroxytryptophan (25-, 50-, 75-, 100 mg/kg) were injected intraperitoneally into freely behaving rats 15 min prior to dark onset, and subsequent effects on sleep-wake activity and cortical brain temperature were determined. L-5-Hydroxytryptophan, but not L-tryptophan, induced dose-dependent changes in sleep-wake activity. During the 12-h dark period, non-rapid eye movement sleep was inhibited in post-injection hours 1-2 by the two lowest L-5-Hydroxytryptophan doses tested, while the two highest doses induced a delayed increase in non-rapid eye movement sleep in post-injection hours 3-12. These highest doses inhibited non-rapid eye movement sleep during the subsequent 12-h light period. The finding that L-5-Hydroxytryptophan, but not L-tryptophan, induced a dose-dependent and long-lasting decrease in cortical brain temperature regardless of whether or not non-rapid eye movement sleep was suppressed or enhanced contributes to a growing list of conditions showing that sleep-wake activity and thermoregulation, although normally tightly coupled, may be dissociated. The initial non-rapid eye movement sleep inhibition observed following low doses of L-5-Hydroxytryptophan may be attributable to increased serotonergic activity since 5-hydroxytryptamine may promote wakefulness per se, whereas the delayed non-rapid eye movement sleep enhancement after higher doses may be due to the induction by 5-hydroxytryptamine of sleep-inducing factor(s), as previously hypothesized. The period of non-rapid eye movement sleep inhibition beginning 12 h after administration of L-5-Hydroxytryptophan doses that increase non-rapid eye movement sleep is characteristic of physiological manipulations in which non-rapid eye movement sleep is enhanced. The results of the present study suggest that the complex effects of 5-HT on sleep depend on the degree and time course of activation of the serotonergic system such that 5-HT may directly inhibit sleep, yet induce a cascade of physiological processes that enhance subsequent sleep.