To optimize secretion and thus production yields, the nature of the SP was the first parameter to modify on heterologous precursor as previously shown using Nuc as a reporter protein. The replacement of the native staphylococcal SP Nuc by the homologous lactococcal SP Usp45 to direct the secretion of Nuc in L. lactis led to an increased SE [25] (Table 3) . On the other hand, the replacement of SP Nuc by SP Usp45 did not enhance the SE of NucT (a truncated mature moiety of Nuc devoid of N-terminal propeptide) suggesting the importance of the propeptide in the SE for Nuc [25] (Table 3) . However, in several cases, the use of a homologous SP (and especially SP Usp45 ) allows a better SE compared to a heterologous one. Screening vectors were thus developed to search for new homologous secretion signals in L. lactis [1, 2] . These screening works offer now a panel of SPs that are suitable for heterologous secretion. However, when compared to SP Usp45, the newly described SPs were less efficient to direct secretion of Nuc [1] . Even after a direct mutagenesis on SP310, one of these new SPs identified using a screening strategy [1] , the enhanced SE was still lower than the one measured with SP Usp45 [26] . However, a recent study by Lindholm et al. showed that a Lactobacillus brevis SP (originated from a Slayer protein) drove the secretion of the E. coli FedF Schematic representation of Nuc cassettes for controlled and targeted production in L. lactis adhesin more efficiently than SP Usp45 [27] . High SE might thus result, at least in part, from good adequacy between the mature protein and the SP used to direct secretion.