Over the past 25 years, metabolic engineering has undergone a remarkable evolution, driven by breakthroughs in synthetic biology, systems biology, and computational modeling. This presentation will trace the field’s transformative milestones, beginning with the early adoption of genome-scale metabolic models and the integration of omics data that enabled precision pathway optimization. Key developments include the advent of CRISPR-based genome editing, enabling rapid strain improvement; the emergence of cell-free systems; and the rise of adaptive laboratory evolution as a powerful tool for phenotype enhancement. Additionally, we explore the expanding role of machine learning in design-build-test-learn cycles and the increasing industrial impact of engineered microbes in producing pharmaceuticals, sustainable chemicals, and biofuels. By highlighting these pivotal advances, this talk will underscore how foundational concepts have matured into robust platforms, paving the way for more predictive, efficient, and sustainable biomanufacturing.
