Abstract
Adaptive laboratory evolution (ALE) has long been used as the tool of choice for microbial engineering applications, ranging from the production of commodity chemicals to the innovation of complex phenotypes. With the advent of systems and synthetic biology, the ALE experimental design has become increasingly sophisticated. For instance, implementation of in silico metabolic model reconstruction and advanced synthetic biology tools have facilitated the effective coupling of desired traits to adaptive phenotypes. Furthermore, various multi-omic tools now enable in-depth analysis of cellular states, providing a comprehensive understanding of the biology of even the most genomically perturbed systems. Emerging machine learning approaches would assist in streamlining the interpretation of massive and multiplexed datasets and promoting our understanding of complexity in biology. This review covers some of the representative case studies among the 700 independent ALE studies reported to date, outlining key ideas, principles, and important mechanisms underlying ALE designs in bioproduction and synthetic cell engineering, with evidence from literatures to aid comprehension.