Advantages of Biobeads
Researchers at PolyBatics mainly engineer biobeads in Escherichia coli, the most prolific microbe. But various types of Bacillus and Lactococcus also make biobeads. The nutrients fed to the microbes determine the composition of the biobeads. “If we feed them glucose, we get polyhydroxybutyrate. If we feed them other substrates, they make different polymers,” says Thompson.
The production of conventional bioseparation resin beads is expensive, laborious, and environmentally unfriendly. Functional proteins are synthesized separately, then captured, washed, and purified. The protein is attached onto a resin bead in a separate process. Toxic solvents are required to make the resin bead and attach proteins to its surface. In contrast, PolyBatics’ method uses simple sugars, salts, and buffers to make completely functional beads.
Moreover, the microbes used by PolyBatics create the bead and attached protein simultaneously in a cost-effective system, Thompson says. The lead product in the company’s pipeline, PolyBindZ, is a disposable replacement for agarose immobilized protein A. Standard methods for making protein A-based beads cost up to $15,000 per liter. PolyBatics makes PolyBindZ for a fraction of that cost.
Using protein A as a model, researchers at PolyBatics isolated only the binding region, called the Z domain. Then they cloned the Z domain into a vector to increase binding efficiency. This produces biobeads with an attached protein in a single step. “So the cost of production is less than for conventional resin beads,” says Thompson.
A further advantage of the microbe-based manufacturing system is that multiple proteins can be attached to a biobead. The insertion of hybrid genes programs bacteria to attach multiple components to the biobead. This results in novel combinations of products with broad applications, explains Thompson. For example, beads with both Gold Binding Protein and antibodies could be used in immunochromatography tests. “It’s a very robust platform. All we have to do is change the gene for the functional domain, be it an enzyme or different ligand,” he notes.