Fast-Growing Engineered Microbes: New Concerns for Gain-of-Function Research?

Lei Pei, Markus Schmidt

Research on fast-growing microbes holds promise for many industrial applications, including shortening test and trial times in research and development stages and reducing the operation costs for production. Such microbes can be obtained either by selecting naturally occurring variants or via metabolic engineering approaches, either eliminating 'unnecessary' or adding necessary pathways affecting growth speed in the cell. Here, we review recent research and development of engineered fast-growing strains in industrial biotechology, with a special focus on vaccine production using (synthetic biology) engineered pathogenic strains. We will discuss whether this represents a security concern and whether the industrial biotech sector needs to pay more attention to issues of Gain-of-Function (GoF) while developing and harnessing these fast-growing microbes. We will also shed a light on the use of in-built biosafety circuits as a way to control the propagation of fast-growing strains, including their capacity to survive in the environment. Other possible GoF concerns raised by the publication of research results in this field will be also addressed. In conclusion, judging from the current development from the field, assessing the potential GoF risks on engineered fast-growing microbes does not lead to a clear generalized outcome. We argue that fast growing strains need to be evaluated in combination with their wild type and engineered characteristics, and require always a case-by-case assessment. Monitoring the progress of the field and proactively raising awareness on the GoF issues among the scientists are important for the further development of the field.