Understanding and Exploiting Feedback in Synthetic Biology

Synthetic biology employs traditional engineering concepts in the construction of cells and organisms. One of the most fundamental concepts is feedback, where the activity of a system is influenced by its output. Feedback can imbue the system with a range of desirable properties such as reducing the rise time or exhibiting an ultrasensitive response. Feedback is also commonly found in nature, further supporting the incorporation of feedback into synthetic biological systems. In this review, we discuss the common attributes of negative and positive feedback loops in gene regulatory networks, whether alone or in combination, and describe recent applications of feedback in metabolic engineering, population control, and the development of advanced biosensors. The examples principally come from synthetic systems in the bacterium Escherichia coli and in the budding yeast Saccharomyces cerevisiae, the two major workhorses of synthetic biology. Through this review, we argue that biological feedback represents a powerful yet underutilized tool that can advance the construction of biological systems. ⺠There are important distinctions between feedback in process control and in biology. ⺠Negative, positive, and combined feedback exhibit unique properties. ⺠Feedback can be readily applied to advance the construction of biological systems.