Synthetic Biology Explained

Synthetic biology is a new interdisciplinary area that involves the application of engineering principles to biology. It aims at the (re-)design and fabrication of biological components and systems that do not already exist in the natural world. Synthetic biology combines chemical synthesis of DNA with growing knowledge of genomics to enable researchers to quickly manufacture catalogued DNA sequences andassemble them into new genomes.

Improvements in the speed and cost of DNA synthesis are enabling scientists to design and synthesize modified bacterial chromosomes that can be used in the production of advanced biofuels, bio-products, renewable chemicals, bio-based specialty chemicals (pharmaceutical intermediates, fine chemicals, food ingredients), and in the health care sector as well.

What is the difference between synthetic biology and systems biology? How does genetic engineering fit in?

Systems biology studies complex natural biological systems as integrated wholes, using tools of modeling, simulation, and comparison to experiment. Synthetic biology studies how to build artificial biological systems, using many of the same tools and experimental techniques. The focus is often on taking parts of natural biological systems, characterizing and simplifying them, and using them as components of an engineered biological system.

Genetic engineering usually involves the transfer of individual genes from one microbe or cell to another; synthetic biology envisions the assembly of novel microbial genomes from a set of standardized genetic parts that are then inserted into a microbe or cell.

What are some goals of synthetic biology?

Synthetic biologists are working to develop:

• Standardized biological parts -- identify and catalog standardized genomic parts that can be used (and synthesized quickly) to build novel biological systems;
• Applied protein design -- re-design existing biological parts and expand the set of natural protein functions for new processes;
•  Natural product synthesis -- engineer microbes to produce all of the necessary enzymes and biological functions to perform complex multistep production of natural products; and
• Synthetic genomics -- design and construct a ‘simple’ genome for a natural bacterium.

How does industrial biotechnology fit in?

Industrial biotechnology provides tools to enhance the natural mechanisms of biological processes to efficiently produce enzymes, chemicals, polymers, or even everyday products such as vitamins and fuel. Scientists have studied the genomes of microbes to identify biological processes that can replace chemical reactions to make new products, cleaner manufacturing operations, and reduce the number of production steps.

For example, by harnessing the natural power of enzymes or whole cell systems, and using sugars as the feedstock for product manufacturing, industrial biotech companies can work with nature to help us move from a petroleum-based economy to a “bio-based economy.”

Industrial biotechnology innovations are now successfully competing with and replacing traditional petrochemical manufacturing processes. Companies that adopt industrial biotechnology find they can cut costs, reduce pollution and their carbon footprint, and increasing profitability.

Industrial biotech scientists and companies have been utilizing forms of synthetic biology for years, including gene splicing, metabolic engineering and directed evolution. Microorganisms that are engineered are used in closed fermentation vats to produce the end products desired. Genetically enhanced microbes (GEMs) are regulated by the Toxic Substances Control Act.

Examples of synthetic biology companies:

Commercial firms that sell synthetic DNA (oligonucleotides, genes, or genomes) to users are DNA synthesis companies, including ATG:biosynthetics, Blue Heron Biotechnology, DNA 2.0, GENEART and Genomatica.

Leading consumer companies of the DNA that are building novel biological systems for bioproducts, biofuels, and the healthcare sector include Amyris Biotechnologies, Inc., Codexis, Genencor (A Division of Danisco), Life Technologies, Genomatica, Qteros, CODA Genomics, Modular Genetics, DNA2.0, Inc., Verdezyne, DSM, Myriant, Gevo, Inc., LS9, Inc., OPX Biotechnologies, Solazyme and Synthetic Genomics, Inc.

What are some synthetic biotechnology breakthroughs?

The 1970s and 1980s saw the emergence of genetic engineering for environmental purposes, such as  bioremediation. A bacterium able to digest petroleum components was developed. In fact the first biotech patent was for a microorganism for cleanup of oil spills. In 2003, scientists at the J. Craig Venter Institute (JCVI) led by Drs. Smith, Hutchinson and Venter, built in vitro a fully synthetic PhiX174 chromosome in just 14 days and
published their results in the Proceedings of the National Academy of Sciences.

In December 2004, George M. Church of Harvard Medical School and Xiaolian Gio of the University of Houston announced that they had invented a new “multiplex” DNA synthesis technique that will eventually reduce the cost of DNA synthesis to 20,000 base-pairs per dollar.

Early in 2006, Dr. Jay Keasling, director of the Berkeley Center for Synthetic Biology, and three post-doctoral researchers discovered and re-engineered a yeast containing bacterial and wormwood genes into a chemical factory to produce a precursor to artemisinin for use as an inexpensive anti-malarial drug.

In June 2007, the JCVI developed genome transplantation methods to transform one type of bacteria into another type dictated by the transplanted chromosome and published their results in the journal Science.

In January 2008, the JCVI created the first synthetic bacterial genome, Mycoplasma genitalium JCVI-1.0, representing the largest man-made DNA structure (also published in Science). Genome transplantation, synthesis and assembly are essential enabling steps toward the ultimate goal of a fully synthetic, activated cell.

In 2010, scientists at the J. Craig Venter Institute (JCVI) announced the world’s first synthetic life form; the single-celled organism based on an existing bacterium that causes mastitis in goats, but at its core is an entirely synthetic genome that was constructed from three chemicals in the laboratory. The single-cell organism has four “watermarks,” written into its DNA to identify it as synthetic.

It took the Venter Institute 15 years to complete this initial project. Much more work needs to be done before scientists can perfect techniques to synthesize novel genomes for microbes or cells.