Researchers from the J. Craig Venter Institute (JCVI) and Synthetic Genomics, Inc. (SGI) have accomplished the next feat in synthetic biology research—the design and construction of the first synthetic bacterial cell containing the minimal code necessary for life that has been named JCVI-syn3.0.
Using the first synthetic cell, Mycoplasma mycoides JCVI-syn1.0 (created by the same team in 2010), the new bacteria JCVI-syn3.0 was developed through a design, build, and test (DBT) process using genes from JCVI-syn1.0.
The new minimal synthetic cell contains only 531,000 base pairs and just 473 genes making it the smallest genome of any self-replicating organism. By comparison the first synthetic cell, M. mycoides JCVI-syn1.0 had 1.08 million base pairs and 901 genes.
“The entire field of biology has been missing a third of what is essential for life in any given cell,” says Venter, who is chairman of the J. Craig Venter Institute. “As we move up the evolutionary tree we’re probably missing a whole lot more.”
The success in creating JCVI-syn3.0 represents a big step forwards in the field of synthetic biology, that aims to making living things programmable.
A biological cell is very much like a computer—the genome is the software that encodes the instructions of the cell and the cellular machinery is the hardware that interprets and runs the genome software. Major advances in DNA technologies have made it possible for biologists to now behave as software engineers and rewrite entire genomes to program new biological operating systems.
“It doesn’t do anything magical rather than live, eat, and self-replicate,” Venter says. But it is, he says, “the first designer organism in history.”
A paper describing this research is published in the March 25 print version of the journal, Science by lead author Clyde A. Hutchison, III, Ph.D., senior author J. Craig Venter, Ph.D., and senior team of Hamilton O. Smith, MD, Daniel G. Gibson, Ph.D., and John I. Glass, Ph.D.
Even with all the advances that have been made in genomics and synthetic biology, there is still not a single self-replicating cell in which we understand the function of every one of its genes. Toward this goal, the JCVI/SGI team has been working to understand the gene content of a minimal cell—a cell that has only the machinery necessary for independent life.
Since the generation of the first synthetic cell in 2010, the team found ways to drastically speed up the process of building cells from the bottom up. They developed new tools and semi-automated processes for genome synthesis, including more rapid, more accurate, and more robust methods for going from oligonucleotides (small pieces of DNA) to whole chromosomes.
Over the past 10 years whole bacterial chromosome assembly has gone from impossible, to possible in years, to months and now to just weeks with these new methods, which are made available to scientists in this manuscript.
“This paper signifies a major step toward our ability to design and build synthetic organisms from the bottom up with predictable outcomes. The tools and knowledge gained from this work will be essential to producing next generation production platforms for a wide range of disciplines,” said Dr. Gibson, Vice President, DNA Technologies, SGI; Associate Professor, JCVI.
“This important milestone lays the foundation to rationally design and engineer bio-based production systems. For example, we see a very large opportunity to revolutionize the discovery and manufacture of life-saving medicines produced biologically, an ever increasing portion of today’s most innovative medicines” said Oliver Fetzer, SGI CEO.
These are time lapse videos of the minimal cell (JCVI-syn3.0) and the wild type organism from which it was designed (JCVI-syn1.0). Magnified 1500X, this shows the growth of the bacteria over an 8-hour period. The videos show the minimal cells are larger than the organism they were designed from, and grow at about the same rate. Micrographs provided by James Pelletier (MIT Center for Bits and Atoms and Department of Physics) and Elizabeth Strychalski (National Institute of Standards and Technology).