Liquid-Liquid Phase Separation: Unraveling the Enigma of Biomolecular Condensates in Microbial Cells

Abstract

Numerous examples of microbial phase-separated biomolecular condensates have now been identified following advances in fluorescence imaging and single molecule microscopy technologies. The structure, function, and potential applications of these microbial condensates are currently receiving a great deal of attention. By neatly compartmentalizing proteins and their interactors in membrane-less organizations while maintaining free communication between these macromolecules and the external environment, microbial cells are able to achieve enhanced metabolic efficiency. Typically, these condensates also possess the ability to rapidly adapt to internal and external changes. The biological functions of several phase-separated condensates in small bacterial cells show evolutionary convergence with the biological functions of their eukaryotic paralogs. Artificial microbial membrane-less organelles are being constructed with application prospects in biocatalysis, biosynthesis, and biomedicine. In this review, we provide an overview of currently known biomolecular condensates driven by liquid-liquid phase separation (LLPS) in microbial cells, and we elaborate on their biogenesis mechanisms and biological functions. Additionally, we highlight the major challenges and future research prospects in studying microbial LLPS.

Getting Closer to Decrypting the Phase Transitions of Bacterial Biomolecules

“…There are common physical properties of bacterial and eukaryotic proteins (e.g., IDRs, LCRs) that drive the formation of biomacromolecular condensates and their further phase transitions [ 136 ]. The formation of such structures inside different types of cells can help cells to respond to different environmental factors and regulate vital functions and can help to maintain cell fitness.…”

Regulating Phase Transition in Neurodegenerative Diseases by Nuclear Import Receptors

“…The valency and patterning of stickers determine IDR phase behavior. Spacer residues are sequences between stickers; they regulate the material properties of condensates [ 115 , 116 ].…”

“…IDRs can transition between multiple material states on the soluble–phase separated liquid–hydrogel–amyloid spectrum [ 119 ]. Factors that alter multivalent interactions, such as RNA, crowding agents, protein concentrations, temperature, pH, and salt content, can affect droplet formation of these IDR-containing proteins [ 116 ]. In addition, post-translational modifications, including phosphorylation, methylation, ubiquitination, and sumoylation, can change the strength and valency of interactions, thus affecting the LLPS of proteins with IDR [ 116 ].…”

“…Factors that alter multivalent interactions, such as RNA, crowding agents, protein concentrations, temperature, pH, and salt content, can affect droplet formation of these IDR-containing proteins [ 116 ]. In addition, post-translational modifications, including phosphorylation, methylation, ubiquitination, and sumoylation, can change the strength and valency of interactions, thus affecting the LLPS of proteins with IDR [ 116 ]. The proteins that undergo phase separation are discussed in the following section.…”

Beyond Amyloid Fibers: Accumulation, Biological Relevance, and Regulation of Higher-Order Prion Architectures

“…Correspondingly, energy limitation and pH change induces Sup35-GFP to reversibly form SDS-sensitive foci in vivo and in vitro [ 120 ]. Understanding the biological impact of LLPS is an emerging field [ 117 , 121 , 122 ], and evidence is only beginning to be accumulated for the role of LLPS in yeast prion biology. Nonetheless, the possibility that these structures can be accessed in vivo must be considered when interpreting the formation of foci in vivo, especially under conditions of high expression and where the biophysical nature of these assemblies is not investigated.…”