Controlling and exploiting cell-to-cell variation in metabolic engineering

[Display omitted] •Cell-to-cell variation can have a significant impact on metabolic engineering.•Strategies for controlling or even exploiting variation can improve production.•New technologies for quantifying variation will enable innovative approaches. Individual cells within a population can display diverse phenotypes due to differences in their local environment, genetic variation, and stochastic expression of genes. Understanding this cell-to-cell variation is important for metabolic engineering applications because variability can impact production. For instance, recent studies have shown that production can be highly heterogeneous among engineered cells, and strategies that manage this diversity improve yields of biosynthetic products. These results suggest the potential of controlling variation as a novel approach towards improving performance of engineered cells. In this review, we focus on identifying the origins of cell-to-cell variation in metabolic engineering applications and discuss recent developments on strategies that can be employed to diminish, accept, or even exploit cell-to-cell variation.