Building Spatial Synthetic Biology with Compartments, Scaffolds, and Communities

Abstract

Traditional views of synthetic biology often treat the cell as an unstructured container in which biological reactions proceed uniformly. In reality, the organization of biological molecules has profound effects on cellular function: not only metabolic, but also physical and mechanical. Here, we discuss a variety of perturbations available to biologists in controlling protein, nucleotide, and membrane localization. These range from simple tags, fusions, and scaffolds to heterologous expression of compartments and other structures that confer unique physical properties to cells. Next, we relate these principles to those guiding the spatial environments outside of cells such as the extracellular matrix. Finally, we discuss new directions in building intercellular organizations to create novel symbioses.

Robust nonequilibrium pathways to microcompartment assembly

“…Spatial segregation is an ubiquitous strategy in biology for organizing the crowded, active viscera of the cell [1][2][3][4]. Viral capsids exemplify this organization at very small scales, sequestering genetic material from the cytosol and recapturing it for delivery to new hosts.…”

Origins of chemoreceptor curvature sorting in Escherichia coli

“…The components of other vital protein complexes, such as the phosphotransferase system3 and the chemotaxis system4, reside at the cell poles. Determining the molecular mechanisms that drive such spatial organization is crucial not only to understand bacterial physiology but also to engineering cells with novel functionalities5.…”

The Synthetic Biology Toolkit for Photosynthetic Microorganisms

“…Eukaryotes present distinct advantages compared to prokaryotes for synthetic biology. This includes the existence of membrane-enclosed organelles that allow exploitation of separated cellular compartments (Polka et al, 2016), thus permitting the engineering of channeling and compartmentalization of metabolism to enhance overall production rates and limit side reactions for metabolic engineering applications. The existence of multiple genetic systems in eukaryotes (nucleus, mitochondria, and chloroplasts) can also offer new design possibilities and allows exploration of the coordination between the compartments, which plays a major role in numerous fundamental cellular processes and is especially crucial for photosynthesis and respiration.…”