Bacterial Microcompartments: Biomaterials for Synthetic Biology-Based Compartmentalization Strategies.

Synthetic biology (SynBio) presents a new paradigm for how metabolic pathways can be designed, assembled and integrated within a cell. A key aim of SynBio is the development of orthogonal tools that facilitate the expression of heterologous genes and circuits in a non-native host (chassis). Compartmentalization represents one orthogonalization strategy, in particular for metabolic pathways, preventing unwanted protein-protein interactions and competition for resources with native pathways, while sequestering toxic intermediates and providing an appropriate environment to support metabolic channeling. A variety of biomaterials have been investigated for their ability to form intracellular compartments. Particularly versatile examples are bacterial microcompartments (BMCs), protein-based shells that sequester a multitude of metabolic reactions in their native host. These compartments provide a natural template for de novo compartmentalization and offer unprecedented opportunities for bioengineering using SynBio. Here we review BMCs as modular building blocks for a general compartmentalization methodology. We describe their role, structure, and properties and discuss the prospects of using SynBio to assemble and engineer microcompartments. Finally, this review explores the future applications of synthetic BMCs and highlights key areas for further research on these unique structures.

Species-selective killing of bacteria by antimicrobial peptide-PNAs.

Broad-spectrum antimicrobials kill indiscriminately, a property that can lead to negative clinical consequences and an increase in the incidence of resistance. Species-specific antimicrobials that could selectively kill pathogenic bacteria without targeting other species in the microbiome could limit these problems. The pathogen genome presents an excellent target for the development of such antimicrobials. In this study we report the design and evaluation of species-selective peptide nucleic acid (PNA) antibacterials. Selective growth inhibition of B. subtilis, E. coli, K. pnuemoniae and S. enterica serovar Typhimurium in axenic or mixed culture could be achieved with PNAs that exploit species differences in the translation initiation region of essential genes. An S. Typhimurium-specific PNA targeting ftsZ resulted in elongated cells that were not observed in E. coli, providing phenotypic evidence of the selectivity of PNA-based antimicrobials. Analysis of the genomes of E. coli and S. Typhimurium gave a conservative estimate of >150 PNA targets that could potentially discriminate between these two closely related species. This work provides a basis for the development of a new class of antimicrobial with a tuneable spectrum of activity.