Credit: Image by DAI Zhuojun
Bacteria are a common host for producing diverse biologics. The synthesis of recombinant proteins using bacterial hosts entails multiple steps, including culturing, disruption and subsequent isolation and purification of the desired product.
For industrial operations, each step requires a sophisticated and delicate infrastructure to ensure efficiency and product quality. This process is critical for producing molecules in large amounts, but is not flexible or economically suited for small-scale production or characterization of diverse biologics.
Moreover, standard biomanufacturing is unavailable in remote or underdeveloped areas that lack basic infrastructure and technical personnel. Therefore, technologies that support versatile and scalable production of diverse biologics on demand, as well as subsequent analysis and purification, are critically needed.
Professor YOU Lingchong of the Duke University Biomedical Engineering Department and Associate Professor DAI Zhuojun of the Shenzhen Institutes of Advanced Technology of the Chinese Academy of Sciences have addressed this need by developing a cell-material feedback platform that facilitates versatile production along with analysis and purification of diverse proteins and protein complexes.
“The core of our technology is a microbial swarmbot that consists of a stimulus-sensitive polymeric microcapsule encapsulating engineered bacteria. By sensing confinement, the bacteria undergo programmed partial lysis at high local density,” said DAI. “Furthermore, the encapsulating material shrinks in response to the changing chemical environment caused by cell growth, thus squeezing out the protein products released from bacterial lysis”.
This platform is then integrated with downstream modules to enable quantification of enzymatic kinetics, purification of diverse proteins, quantitative control of protein interactions, and assembly of functional protein complexes and multi-enzyme metabolic pathways.
This study shows how cell-material feedback can be used to engineer a modular and flexible platform with sophisticated yet well-defined programmed functions. These properties are essential for a number of applications, such as personalized drug synthesis and accessible biomanufacturing in remote areas. Importantly, the operation is simple and can be conducted after minimal training.
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