Abstract
Nano-pesticides represent a significant technology advancement in modern agricultural, offering improved target specificity and reduced chemical load. However, their potential to induce subtle, sub-lethal disturbance in soil microbial function remains poorly resolved and is not adequately capture by conventional indicators such as microbial diversity, abundance, or bulk enzymatic activity. The central novelty of this review lies in proposing post-translational modifications (PTMs) as functional, early-warning biomarkers for nano-pesticide induced microbial stress, providing a molecular resolution that bridges exposure and ecological outcome. This review critically examines the current evidence on nano-pesticides-microbiome interaction and PTM-centric framework to interpret microbial responses at the protein regulation level. We highlight phosphorylation, acetylation, and ubiquitination regulate microbial stress responses, modulating detoxification enzymes, efflux pumps, and cellular signalling pathways under nanoparticle-induced stress. Unlike prior reviews that emphasize toxicity endpoints or gene-level responses, this work integrates metaproteomic evidence demonstrating PTM enrichment within stress-responsive functional protein groups across real environmental datasets, underscoring their relevance as conserved biomarkers of adaptive and maladaptive responses. By integrating metagenomics with metaproteomic and metabolomics, this review illustrates how PTM profiling enables mechanistic insight into microbial adaptation, functional impairment, and resilience under nano-pesticide pressure. Furthermore, we introduce a systems-level perspective that combines PTM data with computational modelling and AI-assisted bioinformatics to predict microbiome shifts and ecological risk, an approach not previously synthesized within the context of nano-pesticide assessment. Collectively, this review bridges nanomaterial design, microbial molecular regulation, and environmental risk evaluation, and proposes PTM-based assessment as a new paradigm for developing microbiome-safe, eco-compatible nano-pesticides and advancing molecular environmental monitoring strategies.