Optimization in Biological Systems: The Legacy of Engineering Complex Processes

Optimization is an engineering methodology that uses a mathematical formulation of a design problem to support selection of the optimal design among many alternatives subject to realistic constraints. Engineers have been optimizing mechanical, chemical, physiochemical, and computational processes since the beginning of time. Starting from the invention of calculus to the design of the most complex industrial machines of our time, we have been optimizing every aspect of the design, operation and control of such processes. The history of engineering has thus been one with the development and implementation of numerous classical optimization techniques. We have continued the legacy of classical optimization in designing biological processes that leverages the plasticity of living systems inherited through evolution. It enables biotechnologists to steer metabolism to many different directions ranging from strain development for chemicals and materials production, drug targeting in pathogens, prediction of enzyme functions, pan-reactome analysis, modeling interactions among multiple cells or organisms, and understanding human diseases. A growing number of computational strain design procedures relying upon mathematical optimization frameworks have emerged benefiting from the rapid advancements in the reconstruction of genome‐scale metabolic models, thus addressing the challenge of identifying and quantifying genetic/environmental interventions and minimizing the counteractions of the organisms in response to them. These large-scale models together with constraint-based optimization methods represent a key foundational advance in Systems Biology and Metabolic Engineering and are crucial for sustainable development in food, pharmaceuticals and bioproduction of the future.