Rational design of next-generation bioinoculants: Integrating molecular engineering of plant-microbe interactions with advanced formulation strategies.
Microbial bioinoculants are increasingly positioned as key technological enablers of sustainable and climate-resilient agriculture, offering biological routes to enhance nutrient use efficiency, suppress pathogens, and improve crop tolerance to abiotic stress while reducing dependence on synthetic agrochemicals. Despite substantial advances in molecular microbiology, plant-microbe interaction research, and microbial biotechnology, the agronomic performance of commercial bioinoculants remains inconsistent across soils, climates, and cropping systems. This persistent variability reflects a structural disconnect between mechanistic understanding at the molecular scale and the largely empirical design of formulation and delivery technologies. In this review, we argue that next-generation bioinoculants should be reconceptualized as engineered biological systems in which microbial traits are rationally designed and explicitly integrated with advanced formulation architectures. We review recent progress in molecular engineering of plant-associated microbes, including synthetic gene circuits, stress tolerance engineering, metabolic rewiring, and signal-responsive regulatory pathways, and integrate these advances with developments in encapsulation, stimuli-responsive carriers, shelf-life stabilization, and smart delivery matrices. We propose a unifying framework in which formulations function as ecological and physiological interfaces that gate microbial survival, activation, and functional expression in complex agroecosystems. By bridging synthetic biology, materials science, and rhizosphere ecology, this integrated design paradigm provides a pathway toward predictable, high-performance biofertilizers and biopesticides suitable for scalable agricultural deployment.