Resource allocation models: theory and applications in microbial biotechnology

Wild-type cells allocate their limited resources to express proteins that support growth and survival in their natural environments. In contrast, biotechnology aims to maximize key performance indicators such as yield, productivity, or titer. Maximizing performance indicators, however, inevitably encounters physical, biochemical, genetic, and evolutionary constraints that create trade-offs between competing objectives. A central challenge in microbial biotechnology is therefore to align cellular behavior with production goals, which can be achieved by manipulating cultivation conditions and intracellular resource allocation strategies through targeted metabolic engineering or adaptive laboratory evolution. Resource allocation models provide a theoretical framework to understand and guide such optimization efforts. Here, we review the current state of resource allocation modeling, including tools, methods, and theoretical foundations, and discuss their current applications in microbial biotechnology. • Resource allocation models provide a theoretical framework to guide optimization. • Different resource allocation models are explained and their applicability reviewed. • Constraints that limit optimization objectives are context and condition dependent. • The concept of proteome efficiency is discussed in the context of overflow metabolism.