| Summary: | Abstract Background Mango (Mangifera indica L.) faces escalating challenges from increasing drought stress due to erratic climate patterns, threatening yields, and quality. Understanding mango's drought response mechanisms is pivotal for resilience and food security. Results Our RNA-seq analyses unveil 12,752 differentially expressed genes linked to stress signaling, hormone regulation, and osmotic adjustment. Weighted Gene Co-expression Network Analysis identified three essential genes—WRKY transcription factor 3, polyamine oxidase 4, and protein MEI2-like 1—as drought defense components. WRKY3 having a role in stress signaling and defense validates its importance. Polyamine oxidase 4, vital in stress adaptation, enhances drought defense. Protein MEI2-like 1's significance emerges, hinting at novel roles in stress responses. Metabolite profiling illuminated Mango’s metabolic responses to drought stress by presenting 990 differentially abundant metabolites, mainly related to amino acids, phenolic acids, and flavonoids, contributing to a deeper understanding of adaptation strategies. The integration between genes and metabolites provided valuable insights by revealing the correlation of WRKY3, polyamine oxidase 4 and MEI2-like 1 with amino acids, D-sphingnosine and 2,5-Dimethyl pyrazine. Conclusions This study provides insights into mango's adaptive tactics, guiding future research for fortified crop resilience and sustainable agriculture. Harnessing key genes and metabolites holds promise for innovative strategies enhancing drought tolerance in mango cultivation, contributing to global food security efforts.
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