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Peer-reviewedCC BY 4.0Frontiers in Microbiology

Transcriptional control of higher alcohol formation in Saccharomyces cerevisiae: a systems framework linking nutrient sensing, precursor allocation, Ehrlich output, and stress adaptation

Abstract

Higher alcohols are major volatile metabolites produced by Saccharomyces cerevisiae. They are traditionally regarded as end products of the Ehrlich pathway. Growing evidence indicates that higher alcohol formation represents a systemic phenotype shaped collectively by nutrient sensing, amino acid uptake, precursor partitioning, carbon source reprogramming, respiratory metabolism, redox homeostasis, and end-product stress. Therefore, higher alcohols serve not only as key aroma compounds, but also as a model system to investigate how yeast integrates environmental cues, metabolism and cellular homeostasis. This review dissects the transcriptional networks regulating higher alcohol biosynthesis. It summarizes nitrogen catabolite repressors Gln3p/Gat1p and Dal80p/Gzf3p; amino acid sensor proteins Stp1p/Stp2p; aromatic branch activator Aro80p; and regulatory proteins involved in precursor supply and metabolic reprogramming, including Leu3p, Gcn4p, Cat8p, Adr1p, Rds2p, Ert1p and the Hap complex. It further discusses the indirect effects of Pdr1p/Pdr3p, Msn2p/Msn4p, Yap1p, Haa1p and War1p via modulation of membrane integrity, redox balance and stress tolerance. Four functional modules are proposed here: substrate input, precursor supply, Ehrlich pathway output, and tolerance maintenance. Three distinct action modes are distinguished: direct pathway activation, precursor remodeling, and high-yield state preservation. This framework explains the condition-dependence and strain specificity of higher alcohol phenotypes. It provides theoretical guidance for subsequent time-resolved omics, chromatin and metabolic flux analyses.

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BibTeX
@article{chen2026transcriptional,
  title = {{Transcriptional control of higher alcohol formation in Saccharomyces cerevisiae: a systems framework linking nutrient sensing, precursor allocation, Ehrlich output, and stress adaptation}},
  author = {Lu Chen and Yuyang Song and Yanlin Liu and Yi Qin},
  journal = {Frontiers in Microbiology},
  year = {2026},
  month = nov,
  doi = {10.3389/fmicb.2026.1980949},
  url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1980949},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Transcriptional control of higher alcohol formation in Saccharomyces cerevisiae: a systems framework linking nutrient sensing, precursor allocation, Ehrlich output, and stress adaptation
AU  - Lu Chen
AU  - Yuyang Song
AU  - Yanlin Liu
AU  - Yi Qin
PY  - 2026
DA  - 2026/11/02
JO  - Frontiers in Microbiology
DO  - 10.3389/fmicb.2026.1980949
UR  - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1980949
AB  - Higher alcohols are major volatile metabolites produced by Saccharomyces cerevisiae. They are traditionally regarded as end products of the Ehrlich pathway. Growing evidence indicates that higher alcohol formation represents a systemic phenotype shaped collectively by nutrient sensing, amino acid uptake, precursor partitioning, carbon source reprogramming, respiratory metabolism, redox homeostasis, and end-product stress. Therefore, higher alcohols serve not only as key aroma compounds, but also as a model system to investigate how yeast integrates environmental cues, metabolism and cellular homeostasis. This review dissects the transcriptional networks regulating higher alcohol biosynthesis. It summarizes nitrogen catabolite repressors Gln3p/Gat1p and Dal80p/Gzf3p; amino acid sensor proteins Stp1p/Stp2p; aromatic branch activator Aro80p; and regulatory proteins involved in precursor supply and metabolic reprogramming, including Leu3p, Gcn4p, Cat8p, Adr1p, Rds2p, Ert1p and the Hap complex. It further discusses the indirect effects of Pdr1p/Pdr3p, Msn2p/Msn4p, Yap1p, Haa1p and War1p via modulation of membrane integrity, redox balance and stress tolerance. Four functional modules are proposed here: substrate input, precursor supply, Ehrlich pathway output, and tolerance maintenance. Three distinct action modes are distinguished: direct pathway activation, precursor remodeling, and high-yield state preservation. This framework explains the condition-dependence and strain specificity of higher alcohol phenotypes. It provides theoretical guidance for subsequent time-resolved omics, chromatin and metabolic flux analyses.
SN  - 1664-302X
ER  -