ORIGIN AND HISTORICAL BACKGROUND
The term ‘synthetic biology’ was coined by Stéphane Leduc, a French biologist in the year 1912. Arguably, Friedrich Wöhler would have been the first scientist to carry out synthetic biology. In 1828, the German chemist produced urea using ammonium chloride and silver isocyanate. Urea is found in mammals and is the main nitrogen-carrying compound. By synthesising urea, an organic substance from inorganic substances Wöhler had successfully carried out synthetic biology.
1970-1999
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It was not until the 1970s that the term ‘synthetic biology’ started to gain recognition. It was during this period that scientists experimented with genetic engineering.
In the 1980s core molecular tools such as restriction enzymes and PCR (polymerase chain reaction) were developed. With PCR one can create multiple copies of required DNA and restriction enzymes can be used to cleave DNA molecules to help create recombinant DNA. This also increased the use of automated laboratory equipment, which took biological research to a greater scale.
In the 1990s efficacy had grown and scientists used computational tools and DNA sequencing for microbial genome sequencing. This allowed automated DNA sequencing to become faster and more affordable. More scientific techniques had been developed for the analysis of DNA, lipids and proteins which played a crucial role in helping generate the cellular components and their reactions and interactions. This allowed scientists and engineers to study the interactions between cellular components. In 1995, the genome of Escherichia coli was fully sequenced, this helped improve our knowledge of biological systems in cells.
2000-2010
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In the 2000s scientists gained a deeper understanding of bacterial biological networks. With this, they designed a repressilator, a genetic toggle switch and an autoregulatory negative-feedback circuit to help control key functions in cells. They also analysed synthetic networks to understand how certain genes interact to produce diversity within phenotypes. Scientists also used synthetic circuitry tools and molecular biology to reprogram bacteria for specific functions such as producing biofuels and invading cancer cells.
In the early 2000s, scientists could create simple regulatory circuits with their knowledge of cellular components and their interactions that worked similarly to electrical circuits. Massachusetts Institute of Technology (MIT) hosted the first international conference for Synthetic Biology in 2004. The same year, they also hosted the first iGEM competition.
From 2004 to 2007 scientists introduced new parts to circuits to increase complexity. It was at this point that many realized efficient methods to assemble individual genetic parts into complex circuits had not been devised, meaning that new circuits were assembled ad hoc. There was also the lack of efficient methods to analyse genetic part functionality resulting in time-consuming procedures for correcting and redesigning constructed circuits to function properly. Moreover, due to ad hoc, there were many uncharacterized parts of circuits. This meant that parts had to be re-characterization when they were introduced into new circuits. To resolve this issue on storage and assembly, the Registry of Standard Biological Parts (RSBP) was created. RSBP is a public repository that is used to physically store and digitally catalogue genetic parts in a standardized format known as ‘Biobrick’. This allows an easier, methodical assembly of a small part to create larger circuits.
It was in the mid-2000s that synthetic biology began to gain recognition. iGEM played an important role in creating interest in this subject from within universities and the general public. Subsequently, organisations also began to fund. An example would be the Science Foundation, which provided funds for SynBERC (Synthetic Biology Engineering Research Project), the synthetic biology laboratories from several leading academic institutions in the US.
An important development occurred in genome transplant in 2007. Scientists at the J. Craig Venter Research Institute (JCVI) transplanted the complete genome of Mycoplasma mycoides – a species of bacteria into the cytoplasm of another bacteria Mycoplasma capricolum. The new bacteria that was created did not exhibit any of the native genes after cell division.
2011-2020
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During this decade scientists designed a programmable microbial kill switch. This demonstrated how synthetic biology could be used to create novel control mechanisms to manipulate the growth and behaviour of genetically engineered microorganisms.
Metabolic engineering also advanced rapidly during this period. They used genome sequence data and the reduction in DNA synthesis costs allowed scientists to develop multiple synthetic pathway prediction models to identify metabolic routes for the host and enzymatic functions. This method has been used in Escherichia coli for rerouting the amino acid biosynthesis pathway to produce fatty acid-based biodiesel, isobutanol, gasoline and 1,4-butanediol - a bioplastic. Since then synthetic regulation is used in production strains, to control the metabolic pathways in response to environmental conditions or metabolic intermediates.
In 2013, the large-scale production of the antimalarial drug artemisinin commenced. Amyris Inc. licenced yeast that was engineered with optimized artemisinic acid pathway, on a royalty-free basis to Sanofi. In turn, Sanofi agreed to produce and supply the low-cost drug to millions of patients with malaria.