Fastest growing Vmax may soon be E. coli in laboratory experiments
The bacterium E. coli has served as a genetic engineering workhorse since the dawn of the biotech era in the 1970s. The first major biotech product, recombinant human insulin, was produced in E. coli by inserting human DNA coding for insulin into the bacterium.
But a superior replacement will soon be available, according to a study from La Jolla’s Synthetic Genomics Inc.
This bacterium is a genetically engineered strain of Vibrio natriegens, which grows far faster than E. coli. While Vibrio natriegens doubles less than 10 minutes, E. coli takes 20 minutes.
Faster growth means less time waiting for the results of experiments, and faster manufacture of biotech products like insulin, said Daniel Gibson, the study’s senior author.
Researchers from Synthetic Genomics Inc. (SGI) announced the development and extensive engineering of Vibrio natriegens into a next-generation biotechnology host organism Vmax™. Looking to accelerate the pace of discovery and the path to sustainable solutions, the team set out to develop a novel bacterial host that will drastically reduce the amount of time scientists spend on each experiment and workflow and to enhance productivity of the resulting new host.
After screening
for the fastest-growing strain and optimizing methods for introducing DNA into those cells at high efficiencies, the team developed genome engineering tools to improve the performance of Vmax™ for common biotech applications, namely, recombinant protein expression and molecular cloning. These breakthroughs build on expertise gleaned during the creation of the first synthetic cell and first minimal cell and again position SGI at the forefront of synthetic biology.“This work provides a game-changing alternative to E. coli, the organism that has been a laboratory staple for decades, and again highlights the rapid and innovative synthetic biology expertise we’ve developed at SGI. We are in the process of designing and synthesizing new Vmax™ cells that operate at even higher efficiencies and productivity as we move toward a next-generation host for protein production,” said Daniel Gibson, Vice President, DNA Technologies, SGI.
“Despite the known drawbacks and shortcomings, scientists have used E. coli as a laboratory host out of necessity primarily because there have been no suitable alternatives,” pointed out Todd Peterson, CTO at SGI. “We deployed our synthetic biology expertise to develop a new host strain that will drastically improve upon these traditional methods and tools.”
Typical cloning projects using E. coli competent cells span several days starting from the time a cloning process is initiated to the time plasmid DNA is prepared. Cloning strategies employing Vmax™ developed by the SGI team shorten that time to as little as one day.
The advancements described by the team set the stage for commercialization of these next-generation cells for cloning and protein expression by SGI in the coming months. Vmax™ is compatible with most kits, reagents, growth medium, vectors, and procedures already entrenched in laboratories. Making these cells commercially available will accelerate the pace of global biotechnological research, making a far-reaching and lasting impact toward genetic exploration and discovery worldwide.
The paper describing this work is the first peer-reviewed publication of its kind and was published online in Nature Methods by Matthew T. Weinstock, Eric D. Hesek, Christopher M. Wilson, and Daniel G. Gibson.