In parallel, biologists and bioengineers have begun constructing novel multienzyme complexes to alter or improve metabolic capacity.
Such screens have been further abetted by the availability of extensive libraries of bacterial, yeast, and mammalian cells expressing proteins fused to reporters. The technological capacity to perform large-scale microscopy screens of protein localization has made possible cell-biological studies that focus on particular cellular conditions. In fact, observations of such bodies have increased markedly in recent years. However, far from being a unique occurrence, these fibers are just the latest in a growing assortment of intracellular bodies formed by metabolic enzymes. It is unknown whether these fibers are enzymatically active, if they serve as cytoskeletal elements, or if they fulfill other, as yet undetermined, regulatory or structural roles. In 2010, three research groups reported the startling discovery that cytidine triphosphate (CTP) synthase, the enzyme that catalyzes the last and rate-limiting step of de novo CTP biosynthesis, can reorganize into extended intracellular fibers in bacterial, fungal, and animal cells ( Ingerson-Mahar et al. We speculate on models for how such structures form in the first place and why they may be inevitable. The panoply of intracellular protein bodies also raises interesting questions regarding their evolution and maintenance within cells. In this article, we survey intracellular protein bodies formed by metabolic enzymes, asking when and why such bodies form and what their formation implies for the functionality-and dysfunctionality-of the enzymes that comprise them.
Although many enzymes clearly form functional mega-assemblies, it is not yet clear for many recently discovered cases whether they represent functional entities, storage bodies, or aggregates. These proteinaceous bodies range in form from fibers and intracellular foci-such as those formed by enzymes of nitrogen and carbon utilization and of nucleotide biosynthesis-to high-density packings inside bacterial microcompartments and eukaryotic microbodies.
Both focused and large-scale cell biological and biochemical studies have revealed that hundreds of metabolic enzymes across diverse organisms form large intracellular bodies.
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