Fermentation-Promoting Peptides Enhance Yeast Robustness during Very High Gravity Fermentation by Reinforcing Antioxidant Defenses and Modulating Intracellular Metabolism

Abstract Very high gravity (VHG) fermentation imposes multiple stresses that impair yeast performance. The effects of fermentation-promoting peptides and their corresponding amino acids on yeast physiology and metabolism were systematically examined under VHG conditions. Peptide supplementation, particularly LL (Leu-Leu), LLL (Leu-Leu-Leu), and LML (Leu-Met-Leu), significantly enhanced yeast growth and ethanol production compared with free amino acids. Peptide-treated cells exhibited alleviated oxidative stress, as evidenced by reduced intracellular ROS and malondialdehyde (MDA) levels, preservation of mitochondrial membrane potential (ΔΨm), and improved membrane integrity. These improvements were accompanied by elevated activities of CAT, SOD, and GSH-Px, increased GSH accumulation, and a more favorable GSH/GSSG ratio. Metabolomic analysis revealed extensive metabolic adjustments involving amino acid metabolism, central carbon pathways, lipid remodeling, and redox-related processes, collectively supporting cellular energy and stress adaptation. Overall, fermentation-promoting peptides reinforce antioxidant defenses and reprogram intracellular metabolism, thereby improving yeast robustness and fermentation efficiency under VHG conditions.