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Gene Synthesis

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More than 30 years after the first complete gene, a yeast tRNA, was synthesized Har Gobind Khorana and coworkers in 1972 and the synthesis of the first peptide- and protein-coding genes was performed in the laboratories of Herbert Boyer and Alexander Markham, DNA synthesis methods have now become the dominating techniques of modern molecular biology where they play a pivotal role in synthetic biology. Since 2007 synthetic biologists have demonstrated that not only can partial or whole chromosomes of bacteria be transplanted between bacterial cells, but also a whole bacterial chromosome could be successfully synthesized. More recently, in March 2014, research scientists in Jef Boeke's group in the Langone Medical Centre at New York University, reported in a paper in the Journal Science that his team was able to synthesize one of the S. cerevisiae 16 yeast chromosomes, the chromosome III, the researchers named synIII. How was this possible?  The experimental strategy used involved replacing the genes in the original chromosome with synthetic gene versions and finally integrating the finished human made chromosome into a yeast cell. However, the design and creation of 273,871 base pairs of DNA, which contained fewer base pairs than the 316,667 pairs in the original chromosome, was required. These examples illustrate the power of existing gene synthesis techniques enabling the assembly of large DNA and RNA sequences from chemical synthetic oligonucleotide building blocks. As can be verified by reviewing the literature in the field of "Synthetic Biology" current oligonucleotide synthesis and enzymatic gene assembly methods and techniques have now been optimized to the point where small operons, plasmids, and viruses can be constructed from scratch with relative ease. Hughes et al. in 2011 argued that these techniques are quickly becoming a cornerstone of modern molecular and synthetic biology methods.

Biosynthesis Inc. now possesses the specialized technical skills, expertise and equipment to help their customer to build large synthetic DNA and RNA sequences.


Reference

Annaluru, Narayana; et al. (March 27, 2014). "Total Synthesis of a Functional Designer Eukaryotic Chromosome"<http://www.sciencemag.org/content/early/2014/03/26/science.1249252>. Science. doi<http://en.wikipedia.org/wiki/Digital_object_identifier>:10.1126/science.1249252<http://dx.doi.org/10.1126%2Fscience.1249252>. Retrieved 2014-03-28.

Edge MD, Green AR, Heathcliffe GR et al. (August 1981). "Total synthesis of a human leukocyte interferon gene". Nature 292 (5825): 756-62. Bibcode<http://en.wikipedia.org/wiki/Bibcode>:1981Natur.292..756E<http://adsabs.harvard.edu/abs/1981Natur.292..756E>. doi<http://en.wikipedia.org/wiki/Digital_object_identifier>:10.1038/292756a0<http://dx.doi.org/10.1038%2F292756a0>. PMID<http://en.wikipedia.org/wiki/PubMed_Identifier> 6167861<http://www.ncbi.nlm.nih.gov/pubmed/6167861>.

Khorana HG, Agarwal KL, Büchi H et al. (December 1972). "Studies on polynucleotides. 103. Total synthesis of the structural gene for an alanine transfer ribonucleic acid from yeast". J. Mol. Biol. 72 (2): 209-217. doi<http://en.wikipedia.org/wiki/Digital_object_identifier>:10.1016/0022-2836(72)90146-5<http://dx.doi.org/10.1016%2F0022-2836%2872%2990146-5>. PMID<http://en.wikipedia.org/wiki/PubMed_Identifier> 4571075<http://www.ncbi.nlm.nih.gov/pubmed/4571075>.

Hughes RA, Miklos AE, Ellington AD.; Gene synthesis: methods and applications. Methods Enzymol.<http://www.ncbi.nlm.nih.gov/pubmed/21601682> 2011;498:277-309. doi: 10.1016/B978-0-12-385120-8.00012-7.

Itakura K, Hirose T, Crea R et al. (December 1977). "Expression in Escherichia coli of a chemically synthesized gene for the hormone somatostatin"<http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=412251>. Science 198 (4321): 1056-1063. Bibcode<http://en.wikipedia.org/wiki/Bibcode>:1977Sci...198.1056I<http://adsabs.harvard.edu/abs/1977Sci...198.1056I>. doi<http://en.wikipedia.org/wiki/Digital_object_identifier>:10.1126/science.412251<http://dx.doi.org/10.1126%2Fscience.412251>. PMID<http://en.wikipedia.org/wiki/PubMed_Identifier> 412251<http://www.ncbi.nlm.nih.gov/pubmed/412251>.

Shukman, David (27 March 2014). "Scientists hail synthetic chromosome advance"<http://www.bbc.com/news/science-environment-26768445>. BBC News. Retrieved 2014-03-28.


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