L-Serine Biosensor-Controlled Fermentative Production of L-Tryptophan Derivatives by Corynebacterium glutamicum

Lenny Ferrer, Mahmoud Elsaraf, Melanie Mindt, Volker F. Wendisch*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

L-Tryptophan derivatives, such as hydroxylated or halogenated L-tryptophans, are used in therapeutic peptides and agrochemicals and as precursors of bioactive compounds, such as serotonin. L-Tryptophan biosynthesis depends on another proteinogenic amino acid, L-serine, which is condensed with indole-3-glycerophosphate by tryptophan synthase. This enzyme is composed of the α-subunit TrpA, which catalyzes the retro-aldol cleavage of indole-3-glycerol phosphate, yielding glyceraldehyde-3-phosphate and indole, and the β-subunit TrpB that catalyzes the β-substitution reaction between indole and L-serine to water and L-tryptophan. TrpA is reported as an allosteric actuator, and its absence severely attenuates TrpB activity. In this study, however, we showed that Corynebacterium glutamicum TrpB is catalytically active in the absence of TrpA. Overexpression of C. glutamicum trpB in a trpBA double deletion mutant supported growth in minimal medium only when exogenously added indole was taken up into the cell and condensed with intracellularly synthesized L-serine. The fluorescence reporter gene of an L-serine biosensor, which was based on the endogenous transcriptional activator SerR and its target promoter PserE, was replaced by trpB. This allowed for L-serine-dependent expression of trpB in an L-serine-producing strain lacking TrpA. Upon feeding of the respective indole derivatives, this strain produced the L-tryptophan derivatives 5-hydroxytryptophan, 7-bromotryptophan, and 5-fluorotryptophan.

Original languageEnglish
Article number744
JournalBiology
Volume11
Issue number5
DOIs
Publication statusPublished - May 2022

Keywords

  • biosensor
  • bromotryptophan
  • Corynebacterium glutamicum
  • fluorotryptophan
  • hydroxytryptophan
  • indoles
  • metabolic engineering
  • TrpB
  • tryptophan

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