The evolution of gene fusions that result in covalently linked protein domains is widespread in bacteria, where spatially coupling domain functionalities can have functional advantages in vivo. Fusions to integral membrane proteins are less widely studied but could provide routes to enhance membrane function in synthetic biology. We studied the major facilitator superfamily (MFS), as the largest family of transporter proteins in bacteria, to examine the extent and nature of fusions to these proteins. A remarkably diverse variety of fusions are identified and the 8 most abundant examples are described, including additional enzymatic domains and a range of sensory and regulatory domains, many not previously described. Significantly, these fusions are found almost exclusively as C-terminal fusions, revealing that the usually cytoplasmic C-terminal end of MFS protein would the permissive end for engineering synthetic fusions to other cytoplasmic proteins.