Conventional enzyme discovery strategies relying on culturable microorganisms are fundamentally limited,as over 99%of microbes remain uncultured under laboratory conditions.This has constrained access to the vast cata...Conventional enzyme discovery strategies relying on culturable microorganisms are fundamentally limited,as over 99%of microbes remain uncultured under laboratory conditions.This has constrained access to the vast catalytic potential encoded within microbial communities inhabiting extreme,diverse,and underexplored eco-systems.Metagenomics has emerged as a transformative approach to overcome these limitations.This meth-odology rapidly unlocks access to novel enzyme families,offering orders-of-magnitude greater diversity than traditional screening.By integrating sequence-driven and function-driven strategies,metagenomics enables the discovery,characterization,and engineering of next-generation biocatalysts for fermentation-based industries.Hydrolases remain the most extensively studied,with applications in starch processing,dairy fermentation,and lignocellulosic bioconversion.Oxidoreductases,including laccases and alcohol dehydrogenases,contribute to bioethanol production,detoxification,and flavor development,while transferases,lyases,and multifunctional enzymes offer opportunities for efficient synthesis of value-added metabolites and streamlined multi-step pro-cesses.These discoveries not only improve fermentation efficiency but also reduce energy inputs,waste gener-ation,and production costs.Advances in bioinformatics pipelines,coupled with machine learning(ML)and artificial intelligence(AI),now facilitate precise gene prediction,functional annotation,and enzyme design.Despite challenges in heterologous expression due to codon usage,folding inefficiencies,and post-translational requirements,metagenomics holds immense promise.This review synthesizes current progress in enzyme mining and highlights how integrating metagenomics with synthetic biology can drive precision fermentation.This review highlights how metagenomics delivers a significant quantitative advantage,often yielding enzymes with improved stability and efficiency,which fundamentally reduce bioprocess costs and enhance industrial scalability.展开更多
基金supported and funded by the Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University(IMSIU)(grant number IMSIU-DDRSP2602).
文摘Conventional enzyme discovery strategies relying on culturable microorganisms are fundamentally limited,as over 99%of microbes remain uncultured under laboratory conditions.This has constrained access to the vast catalytic potential encoded within microbial communities inhabiting extreme,diverse,and underexplored eco-systems.Metagenomics has emerged as a transformative approach to overcome these limitations.This meth-odology rapidly unlocks access to novel enzyme families,offering orders-of-magnitude greater diversity than traditional screening.By integrating sequence-driven and function-driven strategies,metagenomics enables the discovery,characterization,and engineering of next-generation biocatalysts for fermentation-based industries.Hydrolases remain the most extensively studied,with applications in starch processing,dairy fermentation,and lignocellulosic bioconversion.Oxidoreductases,including laccases and alcohol dehydrogenases,contribute to bioethanol production,detoxification,and flavor development,while transferases,lyases,and multifunctional enzymes offer opportunities for efficient synthesis of value-added metabolites and streamlined multi-step pro-cesses.These discoveries not only improve fermentation efficiency but also reduce energy inputs,waste gener-ation,and production costs.Advances in bioinformatics pipelines,coupled with machine learning(ML)and artificial intelligence(AI),now facilitate precise gene prediction,functional annotation,and enzyme design.Despite challenges in heterologous expression due to codon usage,folding inefficiencies,and post-translational requirements,metagenomics holds immense promise.This review synthesizes current progress in enzyme mining and highlights how integrating metagenomics with synthetic biology can drive precision fermentation.This review highlights how metagenomics delivers a significant quantitative advantage,often yielding enzymes with improved stability and efficiency,which fundamentally reduce bioprocess costs and enhance industrial scalability.
