Abstract
The integration of multi-omics approaches is changing microbial biotechnology towards greater environmental sustainability. This review aims to critically evaluate the application of integrative multi-omics and bioinformatics approaches to elucidate the microbial mechanisms underlying bioleaching, with a particular emphasis on key chemolithoautotrophic bacteria and filamentous fungi. Scientists can now reveal and understand the complex molecular mechanisms that allow microbes to survive in extreme environments that are rich in metal through the integration of genomics, transcriptomics, proteomics, and metabolomics. This review shows how the use of multi-omics approaches reveals the interconnected stress responses in important bioleaching bacteria, such as Acidithiobacillus, and fungi like Trichoderma, establishing a connection between genes and their functions. This comprehensive understanding is achieved through the application of advanced computational technologies. Moreover, this review assesses the bioinformatics pipelines, from genome assembly to differential expression analysis, using tools such as DESeq2, while highlighting how machine learning and metabolic modelling can be used to predict interactions and enhance consortia for practical applications in bioleaching. Challenges such as data complexity and expenses exist; however, the field is on the verge of significant advancements. Emerging technologies, especially single-cell omics and CRISPR-based modifications, offer unmatched accuracy in modifying microbial systems. Ultimately, the combination of advanced omics with complex bioinformatics creates a strong foundation for developing next-generation, high-efficiency microbial strategies for environmental metal recovery from waste.