Unveiling multiple copies of MlaC highlights its multifaceted nature.

The maintenance of the lipid asymmetry (Mla) system plays a critical role in facilitating the transport of phospholipids between the inner and outer membranes of the Gram-negative bacteria. In E. coli, the system consists of six proteins: MlaA-OmpF/C complex (outer membrane), MlaC (periplasm), and MlaFEDB complex (inner membrane). Despite extensive research on the core proteins (MlaFED) of the Mla system, the occurrence of Mla components like MlaA, MlaB, and MlaC in diderm remains uncertain. Therefore, this gap presents a significant opportunity for further investigation, particularly regarding MlaC, which serves as the sole mobile component of the Mla system. This has led to the identification of multiple copies of MlaC in 63 distinct genera of Proteobacteria and related phyla. Interestingly, amongst these genera, the genetic arrangements of the mla operon were observed to be varying and, thus, were further categorized into four distinct groups. The variations among the genetic organization of the mla operons suggest their evolution through various processes, such as duplications, losses, rearrangements, and fusions. Further, the results of this study highlight the MlaC's substrate promiscuity, illuminating new avenues for the Mla system.