FEMS Yeast Research, 18, 2018, foy032 doi: 10.1093/femsyr/foy032 Advance Access Publication Date: 16 March 2018 Minireview MINIREVIEW Yeast 2.0—connecting the dots in the construction of the world’s frst functional synthetic eukaryotic genome I.S. Pretorius 1, ∗, † and J.D. Boeke 2 1 Chancellery, Macquarie University, Sydney, NSW 2109, Australia and 2 Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY 10016, USA ∗ Corresponding author: Chancellery, Macquarie University, Sydney, NSW 2109, Australia. Tel: +61,2,98508645; E-mail: Sakkie.Pretorius@mq.edu.au One sentence summary: The international Synthetic Yeast Genome (Sc2.0) project is discovering the dots that connect basic eukaryotic biology, biodesign, bioengineering and biomanufacturing with a budding bioeconomy of the future. Editor: Jens Nielsen †I.S. Pretorius, http://orcid.org/0000-0001-9127-3175 ABSTRACT Historians of the future may well describe 2018 as the year that the world’s frst functional synthetic eukaryotic genome became a reality. Without the beneft of hindsight, it might be hard to completely grasp the long-term signifcance ofa 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-defning scientifc 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 benefcial products. By joining up the dots between the fndings 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 beneft 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 scientifc achievements and lessons from the past, but that is also focussed on leading the present and helping to secure a brighter future for all. Keywords: biodesign; bioengineering; genome engineering; Saccharomyces cerevisiae; Sc2.0; synthetic biology; synthetic chromosomes; synthetic genome; yeast 2.0 Received: 22 February 2018; Accepted: 15 March 2018 C  FEMS 2018. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the orig- inal work is properly cited. 1 Downloaded from https://academic.oup.com/femsyr/article-abstract/18/4/foy032/4939478 by guest on 15 April 2018