First Minimal Synthetic Bacterial Cell

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 minimal synthetic bacterial cell, JCVI-syn3.0.

Using the first synthetic cell, Mycoplasma mycoides JCVI-syn1.0 (built by this same team in 2010), 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.

A paper describing this research is published in the March 25 print version of the journal, Science by lead author Clyde A. Hutchison, III, PhD, senior author J. Craig Venter, PhD, and senior team of Hamilton O. Smith, MD, Daniel G. Gibson, PhD, and John I. Glass, PhD.

Writing Biological Code

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.

Project Goals

A major goal in synthetic biology is to have the capacity to predictably design and build DNA that produces a cell with new and improved biological functions that do not already exist in nature. Significant advances have been made in DNA design at the gene and pathway level and in engineering bacteriophage genomes. But, 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.

A major outcome of this minimal cell program has been new tools and semi-automated processes for whole genome synthesis. Many of these synthetic biology tools and services are commercially available through SGI-DNA.

Milestones in JCVI Synthetic Biology Research and Policy

Funding

This work was funded by SGI, the JCVI endowment and the Defense Advanced Research Projects Agency’s Living Foundries program, HR0011-12-C-0063.

Principal Investigator

Note on Data

The JCVI-syn3.0 sequence has been deposited in Genbank under the accession number CP014940. You can access the supplementary material for the paper by clicking on the link at the end of the text. Note that in addition to Materials and Methods, Supplementary Figures, Supplementary Tables, and References, there is also a link to an Excel Spreadsheet named Database S1. This spreadsheet gives detailed information about the genes of JCVI-syn3.0. The coordinates of each gene on the M. mycoides JCVI-syn1.0 sequence are listed (Genbank accession number CP002027). There is also information about gene annotation, and a column listing the complete amino acid sequence of each protein gene product.

Related Research

Related

Publications

Synthetic chromosomes, genomes, viruses, and cells.
Cell. 2022-07-21; 185.15: 2708-2724.
PMID: 35868275
Genetic requirements for cell division in a genomically minimal cell.
Cell. 2021-04-29; 184.9: 2430-2440.e16.
PMID: 33784496

Principal Investigator

Note on Data

The JCVI-syn3.0 sequence has been deposited in Genbank under the accession number CP014940. You can access the supplementary material for the paper by clicking on the link at the end of the text. Note that in addition to Materials and Methods, Supplementary Figures, Supplementary Tables, and References, there is also a link to an Excel Spreadsheet named Database S1. This spreadsheet gives detailed information about the genes of JCVI-syn3.0. The coordinates of each gene on the M. mycoides JCVI-syn1.0 sequence are listed (Genbank accession number CP002027). There is also information about gene annotation, and a column listing the complete amino acid sequence of each protein gene product.

Related Research

Related

21-Jul-2022
Press Release

Synthetic genomics advances and promise

Advances in DNA synthesis will enable extraordinary new opportunities in medicine, industry, agriculture, and research

20-Jan-2022
Press Release

Scientists develop most complete whole-cell computer simulation model of cell to date

J. Craig Venter Institute model organism-minimal cell platform provides robust tools for exploring first principles of life, design tools for genome

29-Mar-2021
Press Release

Genes necessary for cell division in modern bacterial cells identified

Discovery may help shape understanding of primitive cell division

20-Aug-2009
Press Release

J. Craig Venter Institute Researchers Clone and Engineer Bacterial Genomes in Yeast and Transplant Genomes Back into Bacterial Cells

New methods allow for the rapid engineering of bacterial chromosomes and the creation of extensively modified bacterial species; should also play key role in boot up of synthetic cell

04-Dec-2008
Press Release

J. Craig Venter Institute Researchers Publish Significant Advance in Genome Assembly Technology

Advance Allows for More Efficient Construction of Synthetic Genomes

24-Jan-2008
Press Release

Venter Institute Scientists Create First Synthetic Bacterial Genome

Publication Represents Largest Chemically Defined Structure Synthesized in the Lab

Team Completes Second Step in Three Step Process to Create Synthetic Organism

28-Jun-2007
Press Release

JCVI Scientists Publish First Bacterial Genome Transplantation Changing One Species to Another

Research is important step in further advancing field of synthetic genomics

13-Nov-2003
Press Release

IBEA Researchers Make Significant Advance in Methodology Toward Goal of a Synthetic Genome

Group Synthesizes Biologically Active Genome of Bacteriophage φX174

IBEA research, funded by Dept. of Energy, is an important advance toward the goal of a completely synthetic genome that could aid in carbon sequestration and energy production

21-Nov-2002
Press Release

IBEA Receives $3 Million Dept. of Energy Grant for Synthetic Genome Development

Hamilton Smith, M.D., Nobel Laureate, Named Scientific Director of IBEA