
Nisha Kumari , BS-MS Student , IISER Berhampur
Semi-Synthetic Cells O
On May 20th, 2010 there was news with the heading “Chemical Synthesis Of A Living Organism”regarding a paper published in the journal Science by Prof. Daniel Gibson and team at the J. Craig Venter Institute, USA. Scientists have been extensively trying to construct “Artificial cells” for the last few decades and this news was a path-breaking achievement in that direction. What are artificial/synthetic cells? By definition, artificial cells are biological cell-like structures that exhibit some of the key characteristics of living biological cells. The concept of artificial cells was first proposed by Dr. Thomas Ming Swi Chang in 1957. Artificial cells can be created via two approaches. The first approach is the bottom-up method in which we start from scratch by assembly of the non-living materials that are part of a living cell; and the second one is the top-down approach in which the non-essential genes are knocked out from the cell or completely replaced by synthetic ones. The cells created using this method can also be referred to as “SemiSynthetic cells”. These cells are a kind of artificial cells but they are not completely artificial. In the semi-synthetic cells there is only “alteration in their genetic material in a way that does not exist naturally”, so they are more akin to the genetically modified organisms (GMOs). In 1995, Dr. Venter and colleagues discovered that the parasitic bacterium Mycoplasma genitalium, which is among the simplest living organisms known, has only 517 genes. This small sized genome was an inspiration for scientists to develop “minimal cells”, that is, cells whose genome only encodes a minimal set of genes necessary for survival. The idea of minimal cells eventually moulded the way for semi- synthetic cells. In 2010, the first semi-synthetic cell was produced at the Craig Venter institute. The scientists there first “decoded” the genetic material (DNA) of a bacterium, Mycoplasma mycoides, by DNA sequencing. Then, they chemically copied the genetic information, consisting of about 1.1 million base pairs, and created a new “synthetic chromosome” assembled inside a yeast cell. Later this synthetic chromosome was mobilized (transformed) into a cell from a closely related bacterial species, Mycoplasma capricolum. As soon as the synthetic chromosome was incorporated into the cell, the cell read it as a computer reads a software, rebooting its genetic information with the new DNA. This will then lead to the production of new proteins that are characteristic of the synthetic DNA it now harbours. Along with the attempts of creating artificial cells, scientists are also putting efforts in the synthesis of Unnatural Base Pairs (UBPs) which will expand the genetic alphabets (genetic code). There was an article in the ‘Journal of the American Chemical Society’, published on November 12th, 2018. This article reported the success of scientists who developed a family of unnatural base pairs. For these UBPs, the base pairing is mediated by hydrophobic and packing forces in place of complementary hydrogen bonding. Using these UBPs, we can create semi-synthetic organisms (SSOs) that would have an entirely different type of genetic material that can store increased genetic information and use it to produce proteins containing non-canonical amino acids. Artificial cells have a wide range of applications in synthetic science which includes regenerative medicine, biomedical research, cancer therapy, pollution control, bio-fuel production and much more. Apart from these, by combining the ideas of construction of artificial cells from the basic molecules and adding up these UBPs to form a completely new kind of organism can shed more light about evolution and the origin of life. Despite the impressive progress to date, there is still a wide gap between artificial cells and biological cells. Even though artificial cells potentially harbour a multitude of merits, ethical and environmental concerns are to be addressed satisfactorily before their widespread use so that these cells and their products shall not be a threat to the environment and other organisms. Then there is the ethical concern of “Do scientists have the right to create life and play God?” Dilemma !
References
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2. Justo Corti Varela European Journal of Risk Regulation · September 2010 DOI: 10.1017/S1867299X00000428
3. Can Xu et al J Am Chem Soc. 2018