Tryptophan Derivatives by Saccharomyces cerevisiae EC1118: Evaluation, Optimization, and Production in a Soybean-Based Medium

Int J Mol Sci. 2021 Jan 5;22(1):472. doi: 10.3390/ijms22010472.

Abstract

Given the pharmacological properti es and the potential role of kynurenic acid (KYNA) in human physiology and the pleiotropic activity of the neurohormone melatonin (MEL) involved in physiological and immunological functions and as regulator of antioxidant enzymes, this study aimed at evaluating the capability of Saccharomyces cerevisiae EC1118 to release tryptophan derivatives (dTRPs) from the kynurenine (KYN) and melatonin pathways. The setting up of the spectroscopic and chromatographic conditions for the quantification of the dTRPs in LC-MS/MS system, the optimization of dTRPs' production in fermentative and whole-cell biotransformation approaches and the production of dTRPs in a soybean-based cultural medium naturally enriched in tryptophan, as a case of study, were included in the experimental plan. Variable amounts of dTRPs, with a prevalence of metabolites of the KYN pathway, were detected. The LC-MS/MS analysis showed that the compound synthesized at highest concentration is KYNA that reached 9.146 ± 0.585 mg/L in fermentation trials in a chemically defined medium at 400 mg/L TRP. Further experiments in a soybean-based medium confirm KYNA as the main dTRPs, whereas the other dTRPs reached very lower concentrations. While detectable quantities of melatonin were never observed, two MEL isomers were successfully measured in laboratory media.

Keywords: LC-MS/MS; MEL biosynthesis; Saccharomyces cerevisiae; kynurenine pathway; soybean; tryptophan extraction; yeast.

MeSH terms

  • Chromatography, Liquid / methods
  • Culture Media / metabolism*
  • Fermentation / physiology
  • Glycine max / metabolism*
  • Humans
  • Kynurenic Acid / metabolism
  • Kynurenine / metabolism
  • Melatonin / metabolism
  • Neurotransmitter Agents / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Signal Transduction / physiology
  • Tandem Mass Spectrometry / methods
  • Tryptophan / metabolism*

Substances

  • Culture Media
  • Neurotransmitter Agents
  • Kynurenine
  • Tryptophan
  • Kynurenic Acid
  • Melatonin