MSU Technologies

Synthetic Bacterial Microcompartment Shell Proteins Derived by Circular Permutation and/or Genetic Fusion

INTRODUCTION

Bacterial microcompartments (BMCs) are organelles used by various bacteria to encapsulate metabolic pathways into a proteinaceous shell. BMCs serve as scaffolds to organize encapsulated enzymes and as physical boundaries to reduce diffusive loss of volatile or toxic intermediates and restrict crosstalk with cytosolic biosynthetic pathways. Because of BMC's attributes (i.e., self-assembling modules, optimization of the reactions in their lumen), they can function as customizable catalytic bioreactors for the production of diverse compounds. The modulation of the microcompartment proteins themselves, such as the introduction of internally and externally fused proteins, greatly expands the functional repertoire of these BMCs.

DESCRIPTION OF THE TECHNOLOGY

Derivates of the bacterial microcompartment shell protein BMC from the myxobacteria Haliangium ochraceum have been engineered to allow for diverse metabolic uses. The shell protein BMC‑H was circularly permuted and this derivative protein, CPH, can completely replace non-modified BMC-H proteins. Proteins of interest can be targeted to the BMC shell by genetic fusion to the C-terminus of CPH or BMC‑H using flexible intervening amino acid linkers. When fused to CPH, the protein is located on the inside of the shell and when fused to BMC‑H, the protein is located on the outside of the shell. This fusion allows for discrete spatial localization and quantitative cargo incorporation for the construction of novel BMC nanoreactors.

FURTHER INFORMATION

Ferlez et al., 2019. A designed bacterial microcompartment shell with tunable composition and precision cargo loading. Metab. Eng. 54 (286-291) https://doi.org/10.1016/j.ymben.2019.04.011

BENEFITS