4.4  Synthetic pan-genomes
Large-scale sequencing studies have unravelled the fundamentals of genetic diversity leading to the concept of a pan-genome (Peter et al., 2018). Similar to minimal genomes, pan-genomes seek industrial workhorse applications by stretching the bounds of what genetic substrates can encode within a functional organism. The laboratory strain S288C, and future minimal genome derivatives, are ultimately restricted in their application and lack many of the genotypic features found in industrial strains that define their utility in niche environments (Warringer et al., 2011). In this context, encoding pan-genomic functionality onto a defined neochromosome will complement the objectives of a minimal genome. For example, additional phenotypic plasticity was added to the Sc2.0 substrate through the pan-genomic bolt-on of a 17th neochromosome (Kutyna et al., 2022). In this example, not only does a potential minimal genome gain from the rationalisation of the Sc2.0 chassis as an engineering platform, but the neo-chromosome provides a mechanism to selectively reintroduce naturally occurring wild-type genomic diversity in an abstracted manner. This approach can be used to drive differential carbon source use but would also be amenable to modifying or modulating many of the minimal genomic attributes of the Sc2.0 platform.
The pan-genomic approach to biodesign has also been shown to integrate well with the SCRaMbLE methodology. This provides the researcher with two techniques, one probabilistically random and one based on active human choices. When both techniques are integrated, they provide a way to combinatorially build large phenotypic diversity from a singular starter platform. SCRaMbLE introduces the large opportunity space to work in concert with the genetic diversity of a defined neo-chromosome, thus directing phenotypic diversity towards user-defined evolutionary outcomes and attributes.
Finally, although these concepts represent good examples of ‘top-down’ and ‘bottom-up’ approaches to engineering yeast for industrial biotechnology, exploring these methods in concert with microbial community dynamics represents a largely untouched and exciting research opportunity.