Nat. Biotechnol. https://doi.org/10.1038/s41587-022-01278-2 (2022)

Researchers using fluorescent proteins to label cellular components benefit from an ever-expanding palette of available colors and properties, but increasing brightness usually comes with decreased photostability. Hirano et al. have circumvented this trend with StayGold, which is an order of magnitude more photostable than other available fluorescent proteins while maintaining optimal brightness. Rather than attempt to re-engineer an existing protein, the authors began with a naturally occurring fluorescent jellyfish protein, CU17S, whose minimal photobleaching made it ideal for development. A V168A mutation improved protein folding and chromophore maturation to create StayGold, which has brightness exceeding that of the commonly used enhanced GFP. Additional engineering created versions suitable for visualizing rearrangements of the endoplasmic reticulum at super-resolution, labeling the mitochondrial matrix and microtubule ends, and monitoring SARS-CoV-2 assembly. Although the dimeric nature of StayGold is a limitation, its fundamental photostability and brightness provides a platform for future development and exemplifies the benefits of combining natural sequence discovery with protein engineering.

Credit: Nature