Abstract
Historians of the future may well describe 2018 as the year that the world's first functional synthetic eukaryotic genome became a reality. Without the benefit of hindsight, it might be hard to completely grasp the long-term significance of a breakthrough moment in the history of science like this. The role of synthetic biology in the imminent birth of a budding Saccharomyces cerevisiae yeast cell carrying 16 man-made chromosomes causes the world of science to teeter on the threshold of a future-defining scientific frontier. The genome-engineering tools and technologies currently being developed to produce the ultimate yeast genome will irreversibly connect the dots between our improved understanding of the fundamentals of a complex cell containing its DNA in a specialised nucleus and the application of bioengineered eukaryotes designed for advanced biomanufacturing of beneficial products. By joining up the dots between the findings and learnings from the international Synthetic Yeast Genome project (known as the Yeast 2.0 or Sc2.0 project) and concurrent advancements in biodesign tools and smart data-intensive technologies, a future world powered by a thriving bioeconomy seems realistic. This global project demonstrates how a collaborative network of dot connectors—driven by a tinkerer's indomitable curiosity to understand how things work inside a eukaryotic cell—are using cutting-edge biodesign concepts and synthetic biology tools to advance science and to positively frame human futures (i.e. improved quality of life) in a planetary context (i.e. a sustainable environment). Explorations such as this have a rich history of resulting in unexpected discoveries and unanticipated applications for the benefit of people and planet. However, we must learn from past explorations into controversial futuristic sciences and ensure that researchers at the forefront of an emerging science such as synthetic biology remain connected to all stakeholders’ concerns about the biosafety, bioethics and regulatory aspects of their pioneering work. This article presents a shared vision of constructing a synthetic eukaryotic genome in a safe model organism by using novel concepts and advanced technologies. This multidisciplinary and collaborative project is conducted under a sound governance structure that does not only respect the scientific achievements and lessons from the past, but that is also focussed on leading the present and helping to secure a brighter future for all.
Highlights
In the era of modern science, hardly a week goes by without a breakthrough discovery somewhere in the world in what is colloquially termed as ‘blue-sky’ research
By joining up the dots between the findings and learnings from the international Synthetic Yeast Genome project and concurrent advancements in biodesign tools and smart data-intensive technologies, a future world powered by a thriving bioeconomy seems realistic. This global project demonstrates how a collaborative network of dot connectors—driven by a tinkerer’s indomitable curiosity to understand how things work inside a eukaryotic cell—are using cutting-edge biodesign concepts and synthetic biology tools to advance science and to positively frame human futures in a planetary context
The diverse range in levels of scientific understanding, skillsets and interpretations amongst these stakeholders makes for a colourful kaleidoscope of viewpoints and concerns about predicted outcomes of basic research in emerging sciences, such as synthetic biology and genome engineering
Summary
In the era of modern science, hardly a week goes by without a breakthrough discovery somewhere in the world in what is colloquially termed as ‘blue-sky’ research. The characteristics that make this yeast such a broadshouldered study model include its relatively short reproduction time (90 min under optimal growth conditions); simple and inexpensive cultivation as stable haploid, diploid and polyploid cells in defined media; efficiency of sporulation and crosshybridisation between two stable opposite mating types (a and α); ease of mutant isolation and mapping; efficacy of genetic transformation, maintenance of multiple copies of circular plasmids as well as chromosomal integration through homologous recombination; rare pathogenicity; relatively small genome size [∼12 Mb (non-redundant) to ∼14 Mb (total) genome carrying ∼6000 genes on 16 chromosomes varying in length from ∼200 to ∼2000 kb]; and availability of chip-based gene deletion libraries (Pretorius 2017a) Was this yeast the first microorganism to be domesticated for the production of fermented foods and beverages in ancient times, it was the first microbe to be observed under the microscope, by Antonie van Leeuwenhoek in the late 1600s, and described as a living biochemical agent of transformation by Louis Pasteur 200 years later. The dots are being connected between the Sc2.0 project and the future of synthetic genomics in the era of ‘Biotech 2.0’—a bioeconomy comprising industry-based biodesign, bioengineering, biomanufacturing and biorobotics, and expected to boom in the years to come
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