Engineering membrane architecture for biotechnological applications

Cellular membranes, predominantly described as a dynamic bilayer, are composed of different lipids, transmembrane proteins, and carbohydrates. Most research on biological membranes focuses on the identification, characterization, and mechanistic aspects of their different components. These studies provide a fundamental understanding of membrane structure, function, and dynamics, establishing a basis for the development of membrane engineering strategies. To date, approaches in this field concentrate on membrane adaptation to harsh conditions during industrial fermentation, which can be caused by temperature, osmotic, or organic solvent stress. With advances in the field of metabolic engineering and synthetic biology, recent breakthroughs include proof of concept microbial production of essential medicines, such as cannabinoids and vinblastine. However, long pathways, low yields, and host adaptation continue to pose challenges to the efficient scale up production of many important compounds. The lipid bilayer is profoundly linked to the activity of heterologous membrane-bound enzymes and transport of metabolites. Therefore, strategies for improving enzyme performance, facilitating pathway reconstruction, and enabling storage of products to increase the yields directly involve cellular membranes. At the forefront of membrane engineering research are re-emerging approaches in lipid research and synthetic biology that manipulate membrane size and composition and target lipid profiles across species. This review summarizes engineering strategies applied to cellular membranes and discusses the challenges and future perspectives, particularly with regards to their applications in host engineering and bioproduction.