4.1 Synthetic yeast genomes
A key early advantage in
synthetic yeast genome design was enabled by Saccharomyces
cerevisiae ’s well-curated and regularly updated genome sequence (Cherry
et al., 2012). This in turn enabled synthetic genome designers the
ability to rapidly derive value and understanding by implementing a
‘build-to-understand’ approach through the construction of a synthetic
yeast genome. The starting material of this synthetic yeast genome was
founded on the haploid laboratory strain, S. cerevisiae S288c and
associated ‘BY’ lineage, with the end goal to ultimately design and
chemically synthesize a modified version (Richardson et al., 2017).
At the beginning of the previous decade, the availability of this
well-characterised reference genome sparked the idea of swapping the
natural genome of S. cerevisiae S288c with a redesigned and
chemically synthesized version without compromising the physiological
fitness of the original host strain (Dymond et al., 2011). In 2019, the
work of an international Synthetic Yeast Genome (Yeast 2.0 or
Sc2.0) consortium culminated in the announcement of the first draft
synthetic set of the 16 linear chromosomes of the ‘BY’ lineage
(Pretorius, 2020). However, since the 2019 announcement, several of
these draft chromosomes still needed to be corrected for growth defects.
With the exception of one chromosome, the ‘debugging’ is now complete
and the publications are currently under review. It is anticipated that
the sequential consolidation of
synthetic chromosomes into a
single cell will accelerate progress toward the ultimate Sc2.0 strain,
which will ultimately contain a radically altered genome. This includes
streamlining and stabilising (removal of transposons, non-essential
introns; and the relocation of all tRNA genes onto a separate,
supernumerary tRNA neochromosome), addition of standardised telomeres, a
‘freed-up’ TGA stop codon, PCR-Tags recognition labels and multiple
LoxPsym sites (Richardson et al., 2017).