Effects of tryptophan and phenylalanine on tryptophol production in Saccharomyces cerevisiae revealed by transcriptomic and metabolomic analyses

Xiaowei Gong; Huajun Luo; Liu Hong; Jun Wu; Heng Wu; Chunxia Song; Wei Zhao; Yi Han; Ya Dao; Xia Zhang; Donglai Zhu; Yiyong Luo

doi:10.1007/s12275-022-2059-2

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Effects of tryptophan and phenylalanine on tryptophol production in Saccharomyces cerevisiae revealed by transcriptomic and metabolomic analyses: Xiaowei Gong ¹, Huajun Luo ², Liu Hong ¹, Jun Wu ¹, Heng Wu ¹, Chunxia Song ², Wei Zhao ¹, Yi Han ¹, Ya Dao ², Xia Zhang ¹, Donglai Zhu ¹, Yiyong Luo ^2,3; Journal of Microbiology 2022;60(8):832-842.
DOI: https://doi.org/10.1007/s12275-022-2059-2
Published online: May 27, 2022

¹R&D Center, China Tobacco Yunnan Industrial Co., Ltd., Kunming 650231, P. R. China, ²Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, P. R. China, ³National R&D Center for Freshwater Fish Processing, College of Life Sciences, Jiangxi Normal University, Nanchang 330022, P. R. China

Corresponding author: Donglai Zhu ,
Yiyong Luo ,

Received: 10 February 2022 • Revised: 2 May 2022 • Accepted: 3 May 2022

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Abstract

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.

Keywords: Saccharomyces cerevisiae, tryptophol production, multiomic analysis, nitrogen catabolite repression, thiamine regulon gene thi4, transamination and decarboxylation

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Effects of tryptophan and phenylalanine on tryptophol production in Saccharomyces cerevisiae revealed by transcriptomic and metabolomic analyses

J. Microbiol. 2022;60(8):832-842. Published online May 27, 2022

DOI: https://doi.org/10.1007/s12275-022-2059-2

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