Synthetic biology moves beyond bacteria and viruses with 'man-made' yeast chromosome

The world's first functional synthetic yeast chromosome has been created in an international seven-year effort.

It is the first time a working chromosome from a eukaryotic organism - one that has cells containing a nucleus - has been artificially created. Synthetic biology's prior milestones were mainly in bacteria or viruses, organisms that do not have nuclei.

Researchers hope that synthetic strains of yeast could eventually be used to produce vaccines or biofuels.

According to lead researcher Professor Jef Boeke, director of New York University Langone Medical Center Institute for Systems Genetics: 'It is the most extensively altered chromosome ever built. But the milestone that really counts is integrating it into a living yeast cell. We have shown that yeast cells carrying this synthetic chromosome are remarkably normal. They behave almost identically to wild yeast cells, only they now possess new capabilities and can do things that wild yeast cannot'.

To make their goal as realisable as possible, the researchers decided to work on one of the smallest chromosomes in brewer's yeast. They chose the 315,000-letter long chromosome III. To further facilitate the task, the team cut out 'junk' DNA — DNA that doesn't code for proteins. This trimmed their synthetic creation — synIII — down to 270,000 letters, without killing the yeast.

The team then changed the order of the gene code somewhat, adding and removing chunks of DNA, using a scrambling technique that shuffled the remaining DNA sequence like a deck of cards. This was a very deliberate process. 'We spent about a year debating what changes we should build into the chromosome so we could really learn something from the experience', Professor Boeke told New Scientist.

To build the final DNA sequence, the team divided the chromosome up into sections that were 750 letters long and could be assembled fairly easily. Sixty undergraduate students then 'stitched' these small sections together.

Finally, Boeke's team inserted the SynIII chromosome into yeast cells, replacing the natural chromosome III. Professor Boeke told BBC News: 'What's really exciting about it is the extent to which we have changed the sequence and still come out with a happy, healthy yeast at the end'.

The synthesis of chromosome III is the first stage of an international project to synthesise yeast's entire genome. Teams at several institutions in the USA, Imperial College London (UK), Tianjin University and BGI-Shenzhen (China) are each tackling one of brewer's yeast's 16 chromosomes.

The scientists say an entirely synthetic yeast genome could bring considerable benefits in many applications. Dr Yizhi Cai, a researcher at Edinburgh University and paper co-author, told The Guardian: 'With this technology, we can re-engineer and customise organisms. We could make much sleeker genomes for organisms that would be useful for making biofuels and other industrial applications'.

The study was published in the journal Science.