ClearColi


Researchers using Escherichia coli as a model organism have always had to purify their products thoroughly, due to the dual nature of the microbe—biological workhorse on the one hand, potentially deadly pathogen wielding the endotoxin lipopolysaccharide (LPS) on the other. This step is costly, time-consuming, and rarely complete.
ClearColi is the first-ever line of E. coli that lacks LPS, instead expressing a nontoxic LPS precursor called lipid IVA. “We effectively eliminated endotoxin at the source,” says Uwe Mamat, a microbiologist of the Research Center Borstel in Germany, who was on the team in Ron Woodard’s lab at the University of Michigan that first happened upon a viable E. coli mutant lacking the toxin.


Mamat and his colleagues published their initial results in 2006 (ACS Chem Biol, 1:33-42), after which they were approached by Research Corporation Technologies (RCT), which aims to commercialize technologies coming out of academia. RCT acquired the patent from Woodard’s group and helped the team develop the product, then licensed the technology to Lucigen, which released their first commercial product in May 2013: an LPS-free strain of E. coli for protein production. The researchers also hope to launch a plasmid-production strain by the end of the year, says RCT managing director Chad Souvignier. “The promise all along has been to develop strains that lack endotoxin activity but meet all the other performance characteristics of the strains that people use in their labs,” he says.

MUKOPADHYAY: These cells allow production of proteins in E. coli without need for endotoxin removal steps, which result in loss of yield and increased costs but are not completely effective.

SCHADT: ClearColi has been engineered to eliminate endotoxin and, as a result, much more cleanly produce proteins of interest in large quantities. This has the potential to significantly impact the biologics space.
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