How adaptive evolution reshapes metabolism to improve fitness: recent advances and future outlook

Abstract

Adaptive laboratory evolution (ALE) has emerged as a powerful tool in basic microbial research and strain development. In the context of metabolic science and engineering, it has been applied to study gene knockout responses, expand substrate ranges, improve tolerance to process conditions, and to improve productivity via designed growth coupling. In recent years, advancements in ALE methods and systems biology measurement technologies, particularly genome sequencing and ¹³C metabolic flux analysis (¹³C-MFA), have enabled detailed study of the mechanisms and dynamics of evolving metabolism. In this review, we discuss a range of studies that have applied flux analysis to adaptively evolved strains, as well as modeling frameworks developed to predict and interpret evolved fluxes. These efforts link mutations to fitness-enhanced phenotypes, identify bottlenecks and approaches to resolve them, and address systems concepts such as optimality.

Keywords: Adaptive evolution; fast growth; flux analysis; genotype-phenotype relationship; metabolism.

Figure 1.

Applications of adaptive laboratory evolution (ALE) in strain development for biomanufacturing and in basic science research.

Figure 2.

In adaptive laboratory evolution (ALE) an organism is cultured for many generations under specific conditions of interest. In the process, the fitness (typically growth rate) is improved as beneficial mutations are selected for and accumulate, and metabolism is rewired to facilitate the enhanced phenotype.