Biosynthetic Pathways of Tryptophan Metabolites in Saccharomyces cerevisiae Strain: Insights and Implications.

Hsin-Chieh Kung, Ngoc-Han Bui, Bo-Wun Huang, Nicholas Kiprotich Cheruiyot, Guo-Ping Chang-Chien

Other International journal of molecular sciences 2024 5 citas

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Study Design

Tipo de estudio: In vitro

Intervención: Biosynthetic Pathways of Tryptophan Metabolites in Saccharomyces cerevisiae Strain: Insights and Implications. None
Comparador: Placebo
Dirección del efecto: Positive
Riesgo de sesgo: Unclear

Abstract

Tryptophan metabolites, such as 5-hydroxytryptophan (5-HTP), serotonin, and melatonin, hold significant promise as supplements for managing various mood-related disorders, including depression and insomnia. However, their chemical production via chemical synthesis and phytochemical extraction presents drawbacks, such as the generation of toxic byproducts and low yields. In this study, we explore an alternative approach utilizing S. cerevisiae STG S101 for biosynthesis. Through a series of eleven experiments employing different combinations of tryptophan supplementation, Tween 20, and HEPES buffer, we investigated the production of these indolamines. The tryptophan metabolites were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Notably, setups replacing peptone in the YPD media with tryptophan (Run 3) and incorporating tryptophan along with 25 mM HEPES buffer (Run 4) demonstrated successful biosynthesis of 5-HTP and serotonin. The highest 5-HTP and serotonin concentrations were 58.9 ± 16.0 mg L-1 and 0.0650 ± 0.00211 mg L-1, respectively. Melatonin concentrations were undetected in all the setups. These findings underscore the potential of using probiotic yeast strains as a safer and conceivably more cost-effective alternative for indolamine synthesis. The utilization of probiotic strains presents a promising avenue, potentially offering scalability, sustainability, reduced environmental impact, and feasibility for large-scale production.

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Figures

Figure 1

Overview of biosynthetic pathways for tryptophan metabolites in Saccharomyces cerevisiae, mapping the enzymatic steps from tryptophan to downstream bioactive compounds.

diagram

Figure 2

Metabolite profiling data from yeast strains showing differential production of tryptophan derivatives under varying culture conditions.

chart

Figure 3

Gene expression or enzyme activity data for key enzymes in the tryptophan metabolic pathway in engineered Saccharomyces cerevisiae strains.

chart

Figure 4

Comparative analysis of tryptophan metabolite yields across different yeast strain backgrounds, identifying optimal producers for industrial or therapeutic applications.

chart

Tables

Table 1

	Day 3	Day 4	Day 5
10⁸
10⁹

Table 2

	Day 3	Day 4	Day 5
10⁸
10⁹

Table 3

Runs	Peptone: Tryptophan	Tween 20 (%)	HEPES Buffer (mM)
1	100%:0%	0	0
2	50%:50%	0	0
3	0%:100%	0	0
4		0	25
5		0	100
6		0.1	0
7		0.1	25
8		0.1	100
9		0.2	0
10		0.2	25
11		0.2	100

Table 4

Microbial Species/Strain	Source	Substrate	Concentrations	Ref.
S. cerevisiae STG S101	Purchased	YPD medium (with 100% tryptophan and 25 mM HEPES buffer)	5-HTP = 58.9 ± 16.0 mg L⁻¹Tryptamine = 18.2 ± 1.04 mg L⁻¹Serotonin = 0.0643 ± 0.00272 mg L⁻¹	This study
L. lactis subsp. cremoris (MG 1363)	Purchased	Arginine decarboxylase broth (ADB)	Tryptamine = 0.00Serotonin = 0.71 ± 0.08 mg L⁻¹	[15]
L. lactis subsp. lactis (IL 1403)			Tryptamine = 0.00Serotonin = 0.70 ± 0.05 mg L⁻¹
L. plantarum (FI8595)			Tryptamine = 0.00Serotonin = 0.91 ± 0.07 mg L⁻¹ broth
S. thermophilus (NCFB2392)			Tryptamine = 19.6 ± 0.71 mg L⁻¹ brothSerotonin = 2.70 ± 0.06 mg L⁻¹ broth
S. cerevisiae QA23	Purchased	Synthetic must (200 g L⁻¹ reducing sugars + 300 mg N L⁻¹ assimilable nitrogen), more L-tryptophan (1 mM)	5-HTP = 949 ± 80.3 pg/10⁹Serotonin = 1308 ± 147 pg per 10⁹ cellsMelatonin = ND	[16]
S. cerevisiae P24	Purchased		5-HTP = 935 ± 25.2 pg/10⁹Serotonin = 1037 ± 13.2 pg per 10⁹ cellsMelatonin = 60.83 ± 13.44 pg 10⁹ cells	[16]
P. fluorescens RG11	Isolated from the roots of Red Globe grape cultivar	200 mg L⁻¹ of ¹⁵N double-labeled L-tryptophan	¹⁵N-5-HTP = 0.0181 ± 0.00114 mg L⁻¹¹⁵N-Serotonin = 0.00828 ± 0.00065 mg L⁻¹¹⁵N-acetylserotonin = 0.00866 ± 0.00082 mg L⁻¹¹⁵N-melatonin = 0.00132 ± 0.00012 mg L⁻¹	[14]

References

Melatonin and serotonin effects J. Physiol. Pharmacol., 2007
Enzyme Promiscuity in Serotonin Biosynthesis, From Bacteria to Plants and Humans Front. Microbiol., 2022
Hippocampal ischaemia from accidental 5-Hydroxytryptophan (5-HTP) overdose case report Clin. Neurol. Neurosurg., 2022
Statista Total Global Melatonin Supplements Market in 2016 and a Forecast for 2021
ClinCalc the Top 300 Drugs of 2020
The Potential of Phytomelatonin as a Nutraceutical Molecules, 2018
Naturally occurring melatonin: Sources and possible ways of its biosynthesis Compr. Rev. Food Sci. Food Saf., 2020
Mechanisms of action of probiotics Adv. Nutr., 2019
Sources, formulations, advanced delivery and health benefits of probiotics Curr. Opin. Food Sci., 2020
The many faces of Enterococcus spp.—Commensal, probiotic and opportunistic pathogen Microorganisms, 2021
The genus Enterococcus: Between probiotic potential and safety concerns—An update Front. Microbiol., 2018
Probiotic strains of Lactococcus lactis subsp. lactis produce neuroactive substances J. Hyg. Eng. Des., 2017
Lactobacillus Plantarum LRCC5314 Includes a Gene for a Substance that Stimulates the Secretion of Serotonin Res. Sq., 2021
Endophytic bacterium Pseudomonas fluorescens RG11 may transform tryptophan to melatonin and promote endogenous melatonin levels in the roots of four grape cultivars Front. Plant Sci., 2017
The function of lactic acid bacteria on biogenic amines production by food-borne pathogens in arginine decarboxylase broth Food Sci. Technol. Res., 2012
Intracellular biosynthesis of melatonin and other indolic compounds in Saccharomyces and non-Saccharomyces wine yeasts Eur. Food Res. Technol., 2019
Serotonin Producing Bacteria U.S. Patent, 2022
Microbe-Based Modulation of Serotonin Biosynthesis U.S. Patent, 2016
Saccharomyces cerevisiae Exponential Growth Kinetics in Batch Culture to Analyze Respiratory and Fermentative Metabolism J. Vis. Exp. JoVE, 2018

Used In Evidence Reviews

A Melatonin para Insomnio

A Tryptophan para Insomnio

B 5-HTP para Insomnio

Biosynthetic Pathways of Tryptophan Metabolites in Saccharomyces cerevisiae Strain: Insights and Implications.

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Study Design

Abstract

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