Synthetic Biology, a Primer

Synthetic Chemistry is the bulwark of our chemical industry. It relies on an enormous variety of chemical reactions, specialized reagents and catalysts, to synthesize a complex array of organic molecules: industrial polymers, dyes, fuels,and pharmaceuticals.

Synthetic Biology is a new paradigm that emerged from the recombinant DNA breakthroughs in the 70’s and 80’s: it relies on the biosynthetic capabilities of microbes to carry out the synthesis of complex organic chemical compounds; in principle, any organic compounds.

The properties and biosynthetic capacities of all organisms on our planet are encoded in their genes. Genes are informational molecules, that is, their chemical structure conveys instructions that determine a particular organism’s function or property. All genes, irrespective of their origin, are made of DNA, whose chemical and molecular nature are well established.

Each gene is a defined length of a very long DNA molecule. Each gene is made from the same four constituents; A, C, G, T. The linear arrangement of A, C, G, T creates a code, the so-called genetic code. The code can be viewed as instructions for making the organism’s proteins. The genetic code and the machinery for translating the gene’s information into proteins is universal, consequently, a gene from one organism will be translated into the same protein in any other organism.

Single or clusters of genes can be isolated from any organism, alive or dead, or they can be readily synthesized from their component nucleotides. Whether of biological or wholly synthetic origin, genes can be modified and optimized so that they can be translated into protein(s) in another suitable organism.

By modifying existing genes or by providing new ones (either wholly synthetic or from other organisms), synthetic biologists can enable such organisms to perform novel functions or to produce difficult to come by products.

The strategy of synthetic genomics is modeled after the computer industry; sub-assemblies designed for certain functions can be combined to permit cells to perform even more complex reactions.

Current applications being pursued

  • A living microbe, Mycoplasma genitalium, has been created with an entirely synthetic genome. Aim is to design and synthesize a fully sustainable organism whose synthetic genome could also encode , for example, the machinery to use sunlight and CO2 to manufacture a wide variety of complex industrial chemicals.
  • Engineering microbes capable of converting sugars to higher alcohols and complex hydrocarbons.
  • Artemisinin, a naturally-occurring sesquiterpene lactone that is highly effective against the multi-drug resistant forms of malaria, is difficult to isolate from its natural source, the sweet wormwood plant, and difficult to synthesize. However, it is currently being made in E. coli at an industrial scale.
  • Altering several yeast genes caused a 500-fold increased accumulation of a precursor to steroids. Two genes known to catalyze the last synthetic steps for artemisin in the wormwood plant were copied and after introduction into the yeast the accumulated product was converted to artemisin, a compound readily convertible to the active drug artemisinin.

The field of synthetic biology is in its infancy but is grounded in the application of engineering principles to the existing knowledge and experience of molecular biology. Synthetic biology’s underlying attribute is the ability to modify proteins (enzymes) and thereby the chemical reactions they catalyze by altering the genesthat encode them.

Increased access to the growing number of fully sequenced genomes of even exotic organisms and the ability to move genes from relatively remote or intractable organisms into easily managed microbes will create a new industrial revolution.  As the libraries of individual genes clusters of genes are enlarged, simple organisms or even wholly synthetic organisms will be designed to serve human needs.

Paul Berg is an American biochemist and Professor Emeritus at Stanford University.  He is a Nobel Prize laureate in chemistry and also the 2006 recipient of the Carl Sagan Prize for Science Popularization.  He is a speaker on the subject at Wonderfest 2010, Nov 6.

Click Here to read the counter article on the Chemical Industry, by Richard Zare.