An estimate is worth about a thousand experiments: using order-of-magnitude estimates to identify cellular engineering targets

Kevin James Metcalf, Marilyn F. Slininger Lee, Christopher Matthew Jakobson, Danielle Tullman-Ercek

Biotechnological processes use microbes to convert abundant molecules, such as glucose, into high-value products, such as pharmaceuticals, commodity and fine chemicals, and energy. However, from the outset of the development of a new bioprocess, it is difficult to determine the feasibility, expected yields, and targets for engineering. In this review, we describe a methodology that uses rough estimates to assess the feasibility of a process, approximate the expected product titer of a biological system, and identify variables to manipulate in order to achieve the desired performance. This methodology uses estimates from literature and biological intuition, and can be applied in the early stages of a project to help plan future engineering. We highlight recent literature examples, as well as two case studies from our own work, to demonstrate the use and power of rough estimates. Describing and predicting biological function using estimates guides the research and development phase of new bioprocesses and is a useful first step to understand and build a new microbial factory.