Fighting the battle against evolution: designing genetically modified organisms for evolutionary stability

Synthetic biology has made significant progress in many areas, but a major challenge that has received limited attention is the evolutionary stability of synthetic constructs made of heterologous genes. The expression of these constructs in microorganisms, that is, production of proteins that are not necessary for the organism, is a metabolic burden, leading to a decrease in relative fitness and make the synthetic constructs unstable over time. This is a significant concern for the synthetic biology community, particularly when it comes to bringing this technology out of the laboratory. In this review, we discuss the issue of evolutionary stability in synthetic biology and review the available tools to address this challenge. Evolutionary stability is a key challenge for the advancement of synthetic biology and biotechnology.Epigenetic gene silencing, and not only mutations can render engineered cells useless.There are three major approaches for improving the stability of synthetic genes: reducing mutation; decreasing their metabolic burden; and creating a dependence on the synthetic gene.A complementary approach, using multiple tools, is expected to yield the greatest increase in stability.Most existing tools are only suitable for specific model organisms and are not generic.