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

Int J Mol Sci. 2024 Apr 26;25(9):4747. doi: 10.3390/ijms25094747.

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.

Keywords: 5-hydroxytryptophan; LC-MS/MS; indolamines; melatonin; probiotic strains; serotonin; sustainability; yeast strain.

MeSH terms

  • 5-Hydroxytryptophan* / metabolism
  • Biosynthetic Pathways*
  • Chromatography, Liquid / methods
  • Melatonin / biosynthesis
  • Melatonin / metabolism
  • Saccharomyces cerevisiae* / metabolism
  • Serotonin* / biosynthesis
  • Serotonin* / metabolism
  • Tandem Mass Spectrometry
  • Tryptophan* / metabolism

Substances

  • Tryptophan
  • Serotonin
  • 5-Hydroxytryptophan
  • Melatonin

Grants and funding

This research was funded by the Higher Education Sprout Project (2023~2028), Ministry of Education, Taiwan (R.O.C) and internal funding from the Institute of Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung, Taiwan (R.O.C); the Super Micro Mass Research and Technology Center, Cheng Shiu University, Kaohsiung, Taiwan (R.O.C); and the Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung, Taiwan (R.O.C).