Title Effects of tryptophan and phenylalanine on tryptophol production in Saccharomyces cerevisiae revealed by transcriptomic and metabolomic analyses
Author Xiaowei Gong1, Huajun Luo2, Liu Hong1, Jun Wu1, Heng Wu1, Chunxia Song2, Wei Zhao1, Yi Han1, Ya Dao2, Xia Zhang1, Donglai Zhu1*, and Yiyong Luo2,3*
Address 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
Bibliography Journal of Microbiology, 60(8),832-842, 2022,
DOI 10.1007/s12275-022-2059-2
Key Words Saccharomyces cerevisiae, tryptophol production, multiomic analysis, nitrogen catabolite repression, thiamine regulon gene thi4, transamination and decarboxylation
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.