Complete synthetic yeast organism almost a reality

An international team has rewritten the genetic code of five chromosomes in yeast – one third of the microorganism's entire genome.

The first synthetic yeast chromosome was made three years ago, and the scientists say they are now well on the way to designing and assembling an entire synthetic life form.

'Being able to make such huge changes throughout the genome is very exciting given the extensive use of yeast in modern biotechnology. Having synthetic chromosomes opens up a whole new route to improving production of chemicals, therapeutics and vaccines,' said Dr Tom Ellis from Imperial College London and a member of the Synthetic Yeast Project.

'We will learn a lot about biology along the way, but we can also build superpowers – features you don't see in nature – into the design. It's the ultimate fast lane for evolution.'

The details of the research were published in a special issue of Science devoted to the synthetic yeast genome.

The scientists designed the yeast genome, which is made up of over 12 million base-pairs, on a computer. Unnecessary genetic code was removed in order to make their synthetic organism more stable, making the designed genome eight percent shorter than the original.

They also added a scrambling system into the genome, which can shuffle, delete and duplicate genes when triggered, mimicking the process of evolution but at a much faster pace.

The teams employed a 'design-build-assemble-test-learn' cycle, with chunks of designed chromosome added to the genome sequentially to assess their viability. In this way, 'bugs' in the code can be identified and quickly corrected.

The baker's yeast genome contains 16 chromosomes, each of which can take a year to build. To accelerate the project, each of the labs is working on the chromosomes in parallel. Currently, half of the chromosomes have been assembled, tested and shown to produce healthy yeast cells.

'The project is moving rapidly to completion and it is likely that all the human-designed chromosomes will be fully synthesised by 2018. However, it is still unknown whether all the synthetic chromosomes will work together in a host yeast cell,' said Professor Paul Freemont, also of Imperial College London.

The research builds on work by Craig Venter and others, who have engineered genomes for bacteria and viruses. However, baker's yeast is much closer to mammalian cells – it is a eukaryote and shares around 26 percent of its genes with humans. 'Studying the synthetic genome of yeast can help us to understand in part some of the complexity of the human genome,' added Professor Freemont.

After work is completed on yeast, synthetic biologists plan to build genomes for nematode worms, plants and even mammalian cells. Eventually, the techniques could be used to design genomes for pigs with organs suitable for human transplantation.