APPLICATIONS OF TECHNOLOGY:
- Enables health care, industrial and other commercial uses of protein-based bacterial organelles (bacterial microcompartments (BMCs))
- Modular system for 2- and 3-dimensional scaffolds/compartments
- Defined composition, atomic-resolution structure known
- Robust, programmable encapsulation or polyvalent display of multiple cargo species
- Improves catalyst stability and/or activity, metabolite retention
- Able to tune permselectivity – size and charge, small molecules to proteins
- Amenable to in vivo or ex vivo assembly
- In vitro assembly for rapid prototyping
- Materials properties known, e.g., stable to lyophilization, broad pH range
Berkeley Lab researchers led by Cheryl Kerfeld have developed a technology to functionalize shell proteins with biochemical affinity handles and specific cargo docking sites enabling rapid purification and defined bacterial microcompartment (BMC) cargo loading. The shell modifications can be used to establish BMC architectural principles and enable the design and development of minimal shell systems (2-D scaffolds to 3-D compartments) for applications in health care, environmental remediation, and industrial applications. The affinity handles were used to rapidly screen for in vitro shell formation, revealing a remarkable plasticity in BMC subunit composition.
In nature, BMCs are ensembles of enzymes wrapped in a semi-permeable proteinaceous shell. Identified in the majority of bacterial phyla, these organelles perform distinct, spatially separate metabolic functions that enable their hosts to fix carbon, as in the anabolic carboxysomes, or metabolize substrates like ethanolamine that generate volatile or toxic intermediates, as in the catabolic metabolosomes. Research and development of applications for engineered BMCs include vaccines, drug/gene delivery, microbial production of industrial chemicals, environmental remediation, imaging and sensors.
The new Berkeley Lab technology enables robust, programmable encapsulation of cargo, therefore elevating BMCs to the list of other protein nanoparticles, such as viral-like particles and encapsulins that may be repurposed for industrial, pharmaceutical, and medical uses. In addition, the Berkeley Lab technology may be used to decorate shell exteriors to functionalize the inside and/or outside of BMCs.
DEVELOPMENT STAGE: Proven principle
FOR MORE INFORMATION:
Hagen, A., Sutter, M., Sloan, N., Kerfeld, C. “Programmed loading and rapid purification of engineered bacterial microcompartment shells,” Nature Communications, 2018, 9.
Hagen, A.R., Plegaria, J.S., Ferlez, B., Sloan, N., Aussignargues, C. Burton, R. and Kerfeld, C.A. “In vitro assembly of diverse bacterial microcompartment shell architectures.” NanoLetters 18(11): 7030-7037, 2018.
Sutter, M., Greber, B., Aussignargues, C., Kerfeld, C.A. “Assembly principles and structure of a 6.5 MDa bacterial microcompartment shell.” Science 356, 1293-1297, 2017.
STATUS: Published U. S. Patent Application 15/985,218 (for 2016-150 only). Patent pending for 2017-131. Available for licensing or collaborative research.
SEE THESE OTHER BERKELEY LAB TECHNOLOGIES IN THIS FIELD:
In Vitro Assembly of Bacterial Microcompartments and Related Architectures and Specific Encapsulation of Broad Classes of Materials, 2016-150
Production of Bacterial Microcompartments for Synthetic Biology Applications 2013-014
Directing Biomolecules to Intracellular Microcompartments and Scaffolds IB-2785
Custom Engineered Microcompartments for Enzyme Efficiency, IB-2626