Visualizing the next frontiers in wine yeast research

Abstract

A range of game-changing biodigital and biodesign technologies are coming of age all around us, transforming our world in complex ways that are hard to predict. Not a day goes by without news of how data-centric engineering, algorithm-driven modelling, and biocyber technologies-including the convergence of artificial intelligence, machine learning, automated robotics, quantum computing, and genome editing-will change our world. If we are to be better at expecting the unexpected in the world of wine, we need to gain deeper insights into the potential and limitations of these technological developments and advances along with their promise and perils. This article anticipates how these fast-expanding bioinformational and biodesign toolkits might lead to the creation of synthetic organisms and model systems, and ultimately new understandings of biological complexities could be achieved. A total of four future frontiers in wine yeast research are discussed in this article: the construction of fully synthetic yeast genomes, including minimal genomes; supernumerary pan-genome neochromosomes; synthetic metagenomes; and synthetic yeast communities. These four concepts are at varying stages of development with plenty of technological pitfalls to overcome before such model chromosomes, genomes, strains, and yeast communities could illuminate some of the ill-understood aspects of yeast resilience, fermentation performance, flavour biosynthesis, and ecological interactions in vineyard and winery settings. From a winemaker's perspective, some of these ideas might be considered as far-fetched and, as such, tempting to ignore. However, synthetic biologists know that by exploring these futuristic concepts in the laboratory could well forge new research frontiers to deepen our understanding of the complexities of consistently producing fine wines with different fermentation processes from distinctive viticultural terroirs. As the saying goes in the disruptive technology industry, it take years to create an overnight success. The purpose of this article is neither to glorify any of these concepts as a panacea to all ills nor to crucify them as a danger to winemaking traditions. Rather, this article suggests that these proposed research endeavours deserve due consideration because they are likely to cast new light on the genetic blind spots of wine yeasts, and how they interact as communities in vineyards and wineries. Future-focussed research is, of course, designed to be subject to revision as new data and technologies become available. Successful dislodging of old paradigms with transformative innovations will require open-mindedness and pragmatism, not dogmatism-and this can make for a catch-22 situation in an archetypal traditional industry, such as the wine industry, with its rich territorial and socio-cultural connotations.

Keywords: Saccharomyces cerevisiae; minimal genome; pan-genome; supernumerary neochromosome; synthetic communities; synthetic genome; wine yeast.

Figure 1.

The basic process of winemaking. The from-grapes-to-glass chain of steps are subject to the forces of market-pull and technology-push, which often spark tension between tradition and innovation.

Figure 2.

Saccharomyces cerevisiae is a versatile yeast with a rich fermentation history. Saccharomyces cerevisiae developed a so-called Crabtree-positive carbon metabolism as a highly efficient strategy for sugar utilization that enables energy generation under fermentative or anaerobic conditions and restricts the growth of competing microorganisms by producing toxic metabolites, such as ethanol and carbon dioxide. This yeast species is not only the preeminent model eukaryotic model organism for research but also the most widely used microbe in the biofuel, food, and alcoholic beverage industries, and more recently in the pharmaceutical and biotechnological industries.

Figure 3.

The design and construction of a synthetic S. cerevisiae S288C genome. The Sc2.0 genome is designed to encode a slightly modified genetic code in which (i) all 16 chromosomes contain the same synthetic telomeres; (ii) all nonessential introns and transposons are removed; (iii) all tRNA genes are translocated to a 17th mini-chromosome; (iv) all TGA stop codons are recoded to TAA; (v) PCR-tags and LoxPsym sites are added; and (vi) inconvenient restriction enzyme sites are removed.

Figure 4.

The construction of a synthetic S. cerevisiae pan-genome neochromosome. There is a diverse range of hundreds of S. cerevisiae strains with many displaying distinctive phenotypes. The pan-genome represents the entire set of genes within the S. cerevisiae clade, consisting of a core genome—containing genes shared among all strains within this species—and the dispensable or variable genome, which refers to genes and gene clusters found in two or more strains or to strain-specific genes and gene families.

Figure 5.

The idea of encapsulating a representative synthetic metagenome in a single cell. It is proposed to design and build a synthetic metagenome, which represents multiple grape-related yeast species, in a single S. cerevisiae cell. For example, a synthetic metagenome containing the genes from non-Saccharomyces yeast species could reinforce and/or complement the oenological traits of S. cerevisiae wine strains, such as resilience, fermentation performance, flavour production, and antimicrobial activity to curb spoilage. Conceptually, a wine strain of S. cerevisiae that encapsulates a representative synthetic metagenome could also uncover the complexity of multispecies interactions in wine ferments.

Figure 6.

The idea of synthetic multiplexed yeast consortia with specialization of metabolic tasks. It is proposed to develop yeast consortia to carry out defined roles without the entirety of metabolic burden placed on an individual member. The primary role of the ‘heavy-lifting’ members is to catalyse the rapid, complete, and efficient conversion of grape sugars to ethanol, carbon dioxide, and other minor, but important metabolites without the development of off-flavours. The ‘attributing’ population is responsible for the secondary tasks, such as the biosynthesis of flavoursome compounds. The ‘biosensor’ cells specialize in sensing the conditions in the ongoing fermentation and relay information to the ‘controller’ cells to facilitate automated self-correction activities.

Figure 7.

Guard rails are crucial to frontier science. The convergence of Engineering Biology (Synthetic Biology) and Bioinformational Engineering demands individual and collective responsibility and accountability from researchers. Safety and ethical standards must be embedded in transparent governance structures. The possession of specialist technical expertise entails a special obligation to provide information proactively and to take part in public debate about the uses to which innovations are put.