The Plasma Membrane at the Cornerstone Between Flexibility and Adaptability: Implications for

In the last decade, microbial-based biotechnological processes are paving the way toward sustainability as they implemented the use of renewable feedstocks. Nonetheless, the viability and competitiveness of these processes are often limited due to harsh conditions such as: the presence of feedstock-derived inhibitors including weak acids, non-uniform nature of the substrates, osmotic pressure, high temperature, extreme pH. These factors are detrimental for microbial cell factories as a whole, but more specifically the impact on the cell's membrane is often overlooked. The plasma membrane is a complex system involved in major biological processes, including establishing and maintaining transmembrane gradients, controlling uptake and secretion, intercellular and intracellular communication, cell to cell recognition and cell's physical protection. Therefore, when designing strategies for the development of versatile, robust and efficient cell factories ready to tackle the harshness of industrial processes while delivering high values of yield, titer and productivity, the plasma membrane has to be considered. Plasma membrane composition comprises diverse macromolecules and it is not constant, as cells adapt it according to the surrounding environment. Remarkably, membrane-specific traits are emerging properties of the system and therefore it is not trivial to predict which membrane composition is advantageous under certain conditions. This review includes an overview of membrane engineering strategies applied to