Recoded E. coli Promises More Scalable Weight Loss Drug Production

The manufacturing of weight loss drugs at large scale could get cheaper and more sustainable thanks to an engineered strain of Escherichia coli (E. coli) bacteria.

The fully recoded E. coli, designed to use only 61 codons to synthesize proteins, is now being rolled out as a new method for manufacturing peptides with non-natural chemistries.

That’s according to Constructive Bio, the company that recoded the E.coli and now hopes this synthetic strain will transform the production of some high-volume hard-to-manufacture protein/peptide therapeutics.

“Our key message is that we’re able to produce long peptides containing non-canonical amino acids to deliver therapeutic proteins at scale by biomanufacturing,” explains Rob Salmon, PhD, head of bioprocess at Constructive Bio.

“And our key differentiator is there’s currently a market in, for example, weight loss drugs.”

According to Salmon, glucagon-like peptide-1 (GLP-1) agonists for weight loss are currently produced using chemical synthesis approaches such as solid phase peptide synthesis, which is hard to scale and generates high volumes of toxic waste.

By contrast, the synthetic E. coli strain can potentially produce these peptides using fermentation via standardized industrial processes, he says.

“We want to fit into standardized industrial unit operations and, through that, scale to thousands of liters of product that we can sell to the market,” he explains.

The strain was developed as part of research into reducing the number of codons needed to synthesize proteins in an organism from 64 to 61, allowing slots for three new non-canonical amino acids, according to the company.

Since then, the optimized strain has been taken through some industrial fermentations and demonstrated promising titers, he explains, adding that he will present results at the upcoming Bioprocessing Summit in Boston.

“We’re challenging some of the assumptions from chemists that biology can’t be used to do this,” he says.

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