Secretion of Heterologous Proteins, Gram‐Positive Bacteria,Lactococcus lactis

Abstract Numerous Gram‐positive bacteria are used to produce heterologous proteins allowing easy protein secretion and purification. Among them, lactic acid bacteria (LAB) are interesting hosts since they secrete heterologous protein as both, cell factories and mucosal proteins delivery vectors. For this purpose,Lactococcus lactis, the model LAB, has been widely studied. Here, we review lactococcal expression and secretion systems that have been widely used and developed for heterologous protein production. These systems are based upon improved expression/secretion vectors carrying either inducible or constitutive promoters that allow a tight control of the heterologous protein expression level. These expression systems can include the use of characterized signal sequences as signal‐peptide or synthetic propeptide to drive efficient heterologous protein secretion into the extracellular medium. In parallel, huge knowledge acquired on protein secretion process in model bacteria has allowed us to identify some bottlenecks in processes much as translocation across the membrane, folding and degradation steps. Based on these studies, we describe complementary strategies consisting of host strain modifications to overcome these bottlenecks inL. lactis. Together, these studies are contributed to makeL. lactisand other LABs attractive hosts and efficient cell factories for production and delivery of heterologous secreted proteins.