Genome-wide transcriptomics revealed carbon source-mediated gamma-aminobutyric acid (GABA) production in a probiotic, 9D3.

GABA-producing probiotics present promising opportunities for developing functional foods. Carbon sources have been identified as a critical influence on GABA production. Therefore, this study investigated the holistic metabolic responses and GABA biosynthesis to various carbon sources of 9D3, a proficient GABA producer, using a genome-wide transcriptomic approach. The analysis revealed 414 genes with differential expression responses to altering carbon sources, i.e., glucose, sucrose, and lactose, notably sugar phosphotransferase systems (PTS) (11 genes), indicating carbon source-mediated transcriptional change patterns in 9D3. The integration of transcriptome data with a genome-scale metabolic network (GSMN) revealed that 9D3 displays adaptability by synthesizing GABA as an alternative acid-tolerant mechanism when lactose is used as a carbon source rather than depending on the fatty acid synthesis and the arginine catabolic pathway. The findings of this study offer valuable insights into optimal carbon source utilization and gene expression co-regulation, thereby enhancing the GABA-producing capability of a probiotic and broadening its potential applications in the functional food industry.