Tryptophol (TOL) is a metabolic derivative of tryptophan
(Trp) and shows pleiotropic effects in humans, plants and
microbes. In this study, the effect of Trp and phenylalanine
(Phe) on TOL production in Saccharomyces cerevisiae was determined,
and a systematic interpretation of TOL accumulation
was offered by transcriptomic and metabolomic analyses.
Trp significantly promoted TOL production, but the output
plateaued (231.02−266.31 mg/L) at Trp concentrations ≥ 0.6
g/L. In contrast, Phe reduced the stimulatory effect of Trp,
which was strongly dependent on the Phe concentration. An
integrated genomic, transcriptomic, and metabolomic analysis
revealed that the effect of Trp and Phe on TOL production
was mainly related to the transamination and decarboxylation
of the Ehrlich pathway. Additionally, other genes, including
thiamine regulon genes (this), the allantoin catabolic
genes dal1, dal2, dal4, and the transcriptional activator gene
aro80, may play important roles. These findings were partly
supported by the fact that the thi4 gene was involved in TOL
production, as shown by heterologous expression analysis. To
the best of our knowledge, this novel biological function of thi4
in S. cerevisiae is reported here for the first time. Overall, our
findings provide insights into the mechanism of TOL production,
which will contribute to TOL production using metabolic
engineering strategies.
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