During the past few decades, it's become clear that many enzymes evolved not only to act as specific, finely tuned and carefully regulated catalysts, but also to perform a second, completely different function in the cell. In general, these moonlighting proteins have a single polypeptide chain that performs two or more distinct and physiologically relevant biochemical or biophysical functions. This mini-review describes examples of moonlighting proteins that have been found within the past few years, including some that play key roles in human and animal diseases and in the regulation of biochemical pathways in food crops. Several belong to two of the most common subclasses of moonlighting proteins: trigger enzymes and intracellular/surface moonlighting proteins, but a few represent less often observed combinations of functions. These examples also help illustrate some of the current methods used for identifying proteins with multiple functions. In general, a greater understanding about the functions and molecular mechanisms of moonlighting proteins, their roles in the regulation of cellular processes, and their involvement in health and disease could aid in many areas including developing new antibiotics, predicting the functions of the millions of proteins being identified through genome sequencing projects, designing novel proteins, using biological circuitry analysis to construct bacterial strains that are better producers of materials for industrial use, and developing methods to tweak biochemical pathways for increasing yields of food crops.

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