Drawing on the Past to Shape the Future of Synthetic Yeast Research

Abstract

Some years inspire more hindsight reflection and future-gazing than others. This is even more so in 2020 with its evocation of perfect vision and the landmark ring to it. However, no futurist can reliably predict what the world will look like the next time that a year's first two digits will match the second two digits-a numerical pattern that only occurs once in a century. As we leap into a new decade, amid uncertainties triggered by unforeseen global events-such as the outbreak of a worldwide pandemic, the accompanying economic hardship, and intensifying geopolitical tensions-it is important to note the blistering pace of 21st century technological developments indicate that while hindsight might be 20/20, foresight is 50/50. The history of science shows us that imaginative ideas, research excellence, and collaborative innovation can, for example, significantly contribute to the economic, cultural, social, and environmental recovery of a post-COVID-19 world. This article reflects on a history of yeast research to indicate the potential that arises from advances in science, and how this can contribute to the ongoing recovery and development of human society. Future breakthroughs in synthetic genomics are likely to unlock new avenues of impactful discoveries and solutions to some of the world's greatest challenges.

Keywords: biodesign; biodiversity; biofoundry; consilience; engineering biology; fermentation; scientific method; synthetic genomics; timeline; yeast.

Figure 1

The scientific method, underpinned by the principles of consilience, was perhaps the single most important development in modern history. This approach entails systematic observation, measurement, and experiment, and the formulation, testing, and modification of hypotheses by drawing on data and evidence from independent, unrelated academic disciplines—from science, technology, engineering, mathematical, and medical (STEMM) fields of research to the humanities, arts, and social sciences (HASS).

Figure 2

The budding yeast, Saccharomyces cerevisiae, has emerged as the most popular eukaryotic model organism to develop and test new genetic technologies and industrial applications. These attributes include its relatively short reproduction time; simple and inexpensive cultivation as stable haploid, diploid and polyploid cells in defined media; efficiency of sporulation and cross-hybridisation between two stable opposite mating-types; 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; and availability of gene deletion libraries consisting of strains carrying unique DNA barcodes that mark each deletion [19,57].

Figure 3

The discovery of DNA is one of our greatest scientific achievements. The history of DNA science consists of a series of bright ideas and profound breakthroughs that led to the current read-write-edit paradigm shift.

Figure 4

Key milestones in terms of the synthesis of viral and bacterial genomes inspired the idea to chemically synthesise the 16 chromosomes of the yeast Saccharomyces cerevisiae and replace the native chromosomes with the synthetic chromosomes.

Figure 5

The application of design-build-test-learn (DBTL) biological engineering cycle can be accelerated in high-throughput, automated biofoundries with robotic workflows and technology synthetic biology platforms. Recent rapid advances in high-throughput DNA sequencing (reading) and DNA synthesis (writing and editing) techniques are enabling the design and construction of new biological parts (genes), devices (gene networks), and modules (biosynthetic pathways), and the redesign of biological systems (cells and organisms) for useful purposes.