The cysteine regulatory complex from plants and microbes: what was old is new again

[Display omitted] ► Physical organization of enzymes plays an important role in metabolism. ► Two enzymes in plants and bacteria form the cysteine regulatory complex (CRC). ► In plants, the CRC modulates cysteine biosynthesis in response to sulfur state. ► Recent insights on this multi-enzyme complex suggest new research directions. The physical organization of enzymes in metabolism is an old concept being revisited by new experimental approaches. In plants and microbes, the enzymes of cysteine biosynthesis—serine acetyltransferase (SAT) and O-acetylserine sulfhydrylase (OASS)—form a bi-enzyme complex called the cysteine regulatory complex (CRC), which likely plays a role in modulating cysteine biosynthesis in response to sulfur nutrient state. Structural and biochemical studies of SAT and OASS as individual enzymes and recent advances in structural, biophysical, and in vivo analysis of the CRC provide new insights on the function of this macromolecular assembly in plants and microbes and opens biotechnology and pharmaceutical opportunities for future exploration.