Biological redesign of virus particles for a new era of catalytic materials

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Montana State University - Bozeman, College of Letters & Science


Biology has designed a suite of compartments and barriers that confine fundamental biochemical reactions. Such barriers include the membrane-bound organelles but also a suite of protein-based compartments that architecturally and chemically integrate catalytic processes. These compartments co-polymerize from multiple protein subunits to form polyhedral structures that spatially separate enzymatic processes. Protein compartments confine volatile intermediates, trap toxic reaction products, and co-localize multiple enzymatic processes for catalytic enhancements. The protein-based compartments represent, advantageously, a combination of form and function that has inspired the synthesis of new, designer materials. The self-assembly of cage-like structures, the structures of which are reminiscent of the compartments, has been used for the directed encapsulation of active enzymes. We have used the capsid from bacteriophage P22, as a nanocontainer for directing the encapsulation of a variety of gene products, including active enzymes. The P22 capsid assembles from a coat protein (CP) and a scaffold protein (SP) which templates its assembly. Using the simplicity of the P22 expression system, a strategy was developed and implemented for the directed encapsulation of an active, [NiFe] hydrogenase. We hypothesized and proved the enzyme active site needed to be matured by accessory proteins found within the expression host. A two plasmid expression system was designed, where the hydrogenase cargo was under the control of a different inducer than the P22 CP. The [NiFe]-hydrogenase is a heterodimer and each enzyme subunit was fused to different SP. The resultant packaging of the two SP fusions, with the hydrogenase large and small subunits fused to them stabilized a weak heterodimeric structure. Remarkably, the stabilizing effects of the capsid allowed us to probe the infrared signatures associated with the hydrogenase active site. Finally, the progress made here in developing a virus capsid for H2 production left room to build increased complexity into the P22-Hydrogenase system while also taking inspiration from the innate, biological function of the hydrogenase. We incorporated a cytochrome/cytochrome reductase pair to drive H 2 production using NADH. These designs, built at the molecular level, represent inherently renewable catalysts that pave the way for a new era of catalytic materials synthesized entirely by biology.




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