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

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.