Digital and analog gene circuits for biotechnology

Biotechnology offers the promise of valuable chemical production via microbial processing of renewable and inexpensive substrates. Thus far, static metabolic engineering strategies have enabled this field to advance industrial applications. However, the industrial scaling of statically engineered microbes inevitably creates inefficiencies due to variable conditions present in large-scale microbial cultures. Synthetic gene circuits that dynamically sense and regulate different molecules can resolve this issue by enabling cells to continuously adapt to variable conditions. These circuits also have the potential to enable next-generation production programs capable of autonomous transitioning between steps in a bioprocess. Here, we review the design and application of two main classes of dynamic gene circuits, digital and analog, for biotechnology. Within the context of these classes, we also discuss the potential benefits of digital-analog interconversion, memory, and multi-signal integration. Though synthetic gene circuits have largely been applied for cellular computation to date, we envision that utilizing them in biotechnology will enhance the efficiency and scope of biochemical production with living cells.National Institutes of Health (U.S.) (1DP2OD008435)National Institutes of Health (U.S.) (1P50GM098792)National Science Foundation (U.S.) (1124247)United States. Defense Advanced Research Projects AgencyEllison Medical FoundationUnited States. Office of Naval Research (N00014-11-1-0725)United States. Office of Naval Research (N00014-11-1-0687)United States. Office of Naval Research (N00014-13-1-0424)United States. Army Research Office (W911NF-11-1-0281)Presidential Early Career Award for Scientists and EngineersFord Foundatio