Exogenous γ-Aminobutyric Acid (GABA) Alleviates the Trade-Off Between Growth and Andrographolide Accumulation in Andrographis paniculata.

Exogenous γ-aminobutyric acid (GABA) alleviates nitrogen (N) deficiency stress in plants; however, its effects on secondary metabolite biosynthesis in medicinal plants under such conditions remain poorly understood. This study investigated the effects of GABA on the growth and andrographolide biosynthesis in Andrographis paniculata (Chuanxinlian) under low N (LN, 1 mmol L-1 NO3 -) using soilless culture. Our findings indicated that both 5 mmol L-1 GABA and nitrate-N (NN) treatments enhanced plant N accumulation, upregulated photosynthesis and N metabolism, and downregulated secondary metabolism such as flavonoid and andrographolide biosynthesis, consistent with the protein competition model (PCM) and carbon/nutrient balance hypothesis (CNBH). Nevertheless, compared to NN, GABA attenuated the decline in andrographolide content and maintained levels of 14-deoxyandrographolide and dehydroandrographolide. Consequently, GABA preserved the yield of diterpenoid lactones, whereas NN treatment resulted in a significant reduction. Metabolomic analyses revealed similarities between GABA-treated and control plants in glycolysis and the tricarboxylic acid (TCA) cycle. Additionally, transcriptome analysis revealed that upregulated differentially expressed genes (DEGs) in both control and GABA treatments were enriched in sulfur-related metabolism, extracellular signaling pathways, and cyanoamino acid metabolism, suggesting these processes are closely associated with the regulation of andrographolide biosynthesis. The cytochrome P450 enzymes CYP71D11 and CYP76T24 were identified as promising candidates involved in andrographolide biosynthesis. Collectively, these results demonstrate that exogenous GABA not only alleviates N deficiency stress but also mitigates reductions in andrographolide content in Chuanxinlian, suggesting that GABA presents a promising alternative to nitrate fertilizers for achieving high-yield and high-quality production of Chuanxinlian under N-deficient conditions.