DNA writing and synthetic biology go hand in hand. Now, Tierra Biosciences wants to extend that hand to proteins. To do that, they have launched the first online protein ordering platform. Like ordering DNA oligos (or pizza) a scientist can order proteins online by adding them to their cart and then wait for them to arrive at their door.
Tierra’s protein platform is a cell-free system that allows researchers to order proteins of up to 1,000 amino acids. This size, Tierra noted, should be adequate for most circumstances given that the average protein size is 200–300 amino acids.
“The next major biological frontier after genomics is proteins, given their diverse form and function, from converting carbon dioxide to starch to fighting infections in our body,” said Zachary Sun, PhD, co-founder, and CSO of Tierra. “However, there is a lack of expedient research tools and ordering platforms for protein engineers, which can create significant time and cost bottlenecks for critical synthetic biology research.
The technology that underlies the platform was developed by Sun during his graduate work in the lab of Richard Murray, professor of control and dynamical systems and bioengineering at California Institute of Technology and a co-founder of the company. The foundational technology is described in a paper titled, “Linear DNA for Rapid Prototyping of Synthetic Biological Circuits in an Escherichia coli Based TX-TL Cell-Free System,” and published in the journal ACS Synthetic Biology in 2014. The company was started soon after Sun received his degree in 2015.
The cell-free system uses automation and AI to enable protein synthesis that is completely ex vivo. Tierra noted that they can vary three parameters when making proteins: 1) sequence variants, producing and expressing different DNA variants in parallel, 2) cell-free systems, with systems that span Gram-positive, Gram-negative, and eukaryotic species, 3) modifications, with supplementation of cofactors or salts.
Currently, Tierra’s standard product provides 50 microliters of each protein. The concentration of the protein can vary widely, they say, based on the unique properties of each protein and expression efficiency in the system, but the average yield is in the microgram range. The cost for one protein is roughly $600.
What about protein modifications? The cell free system is E. coli based. So, the proteins are expected to have whatever modifications they would have if produced through a typical cloning process in E. coli.
Tierra considers themselves a synthetic biology company and envisions playing a role for other synthetic biology companies in need of quick production of multiple different proteins.
For example, one San Diego based company, Debut Biotech, needed to solve a metabolic engineering question in order to convert sugars into chemicals. To uncover the most efficient metabolic pathway, which involved multiple enzymes, they needed to perform a combinatorial search. They ordered the enzymes from Tierra to test multiple combinations, trying to optimize the enzymes for each step in the pathway.
Another example comes from a synthetic biology company innovating cow-free leather. The company needed to test hundreds of different forms of the protein collagen, experimenting with combinations to optimize material to form leather used to make shoes, versus leather to make a wrist band or a handbag.
Corinna Chen, a partner at Material Impact who joined Tierra as CEO in July of 2021, told GEN that synthetic biology companies should spend their time on product innovation rather than protein production.
Current options for protein production range from expensive contract manufacturers, to kits that can synthesize common peptides in small quantities, to old-fashioned methods of cloning and purification. Tierra—which has an average order size of 54 proteins—is hoping to create a new option of cell-free protein synthesis.
