Engineered proteins as multifunctional materials
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Introduction Proteins are among the pinnacle of polymeric materials. Nature has developed the ability to produce these monodisperse polymers with a palette of 20 amino acid monomers and nearly complete sequence control. This unparalleled level of complexity allows proteins to precisely fold and self-assemble forming not only enzymes and antibodies, but also multifunctional materials with remarkable mechanical, optical, and electronic properties. For decades, scientists and engineers have sought to understand and replicate the complex relationships between structure and processing conditions that governs the properties of these materials.1–3 This work has been carried out by studying and harvesting protein materials from native organisms and, more recently, by engineering biological systems to produce and assemble protein materials. While humans have relied on naturally harvested proteins as tools, textiles, and adhesives for thousands of years, recent advancements in biomedicine (tissue engineering, drug delivery, neural prosthetics, and wound healing) and engineered living materials, as well as the urgent need for sustainable alternatives to synthetic plastics have created an unprecedented demand for the scalable production of engineered protein-based materials with properties and functionality tailored to the specific application. Protein engineering can be employed to encode proteinbased materials with desired properties and functionality.
Recent advances in synthetic biology have further accelerated the pace at which protein materials can be engineered. The design-build-test-learn loop can be used to iteratively evolve proteins with properties and functionality tailored to the desired application (Figure 1). In the design stage, artificial genes encoding modular elements, inspired by those in nature or designed de novo, can be flexibly combined to create new protein block copolymers or to outfit proteins with functional domains such as stimuli-responsive sequences, enzymes, and recognition sites. The build stage comprises of DNA assembly, cloning into organisms, protein expression, purification, and processing. Next, in the test stage, the desired materials properties are frequently measured through conventional characterization methods. This often represents a significant bottleneck as these characterization methods can be time-consuming and require a significant amount of material. Finally, the learn stage utilizes the measured data and any available computational models to provide insight into the structure–property relationship and new potential designs for future iterations. While the design-build-test-learn loop holds great promise, the ability to use this iterative process to engineer protein materials has lagged behind its use in other areas such as natural products, biofuels, and pharmaceuticals. This gap is caused by specific challenges that are faced in the cloning, expression,
Maneesh K. Gupta, Air Force Research Laboratory, USA; [email protected] Drew T. Wagner, Air Force Research Laborator
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