Effects of polyploidization during adaptive evolution in yeasts (PloidYeast)

What if the leftovers from food production — the peels, stalks, and sugars we usually throw away — could be transformed into valuable products like biofuels, sweeteners, or even ingredients for cosmetics and pharmaceuticals? That’s the vision behind our research, and the key to unlocking it lies in a tiny but mighty organism: yeast. Every year, the food industry generates millions of tons of plant-based waste. These subproducts are rich in sugars like xylose and maltose, but most conventional yeasts can’t use them efficiently. That’s where our project comes in. We’re engineering a new generation of yeast — what we affectionately call “Frankenyeasts” — to turn food waste into high-value compounds, helping build a more sustainable and circular bioeconomy. Yeast is already a workhorse in biotechnology. But the strains used today have limitations. To overcome them, we’re exploring a natural evolutionary trick called polyploidization, where yeast multiplies its entire genome. This gives it extra genetic material to adapt and thrive in harsh industrial conditions. Our team has combined eight different yeast species, sequenced and assembled from telomere to telomere (Schweizer et al.’s manuscript in preparation), each with unique traits, to create synthetic auto- and allopolyploids, strains with enhanced adaptive potential. These new strains are being tested under four industrially relevant conditions, including the ability to grow on glucose, xylose, and maltose, sugars commonly found in food subproducts, and low temperatures, a condition of relevance in the brewing industry. We’ve already built a diverse collection of 64 unique strains, 168 allotetraploids, and 8 autotetraploids, and discovered that the mitochondrial genome in the case of allotetraploids, the cell’s energy engine, plays a crucial role in how the strain adapt (Orellana-Muñoz et al.’s manuscript in preparation). By carefully selecting parental strains with compatible nuclear and mitochondrial genomes, we might optimize yeast performance for industrial applications. These polyploids are now undergoing adaptive laboratory evolution, a process that mimics natural selection in the lab. Early results show that polyploidization facilitates adaptation, allowing yeast to evolve quickly to use unconventional carbon sources and tolerate stress. This is a major step toward converting food waste into biofuels, xylitol (a low-calorie sweetener), and other value-added compounds. We’re also preparing to generate the first multiomic datasets — integrating genomics, transcriptomics, proteomics, and metabolomics — to understand the molecular mechanisms behind yeast adaptation. These data will help us build machine learning models to predict which yeast combinations work best for specific industrial goals. The project is approximately 75% completed. To tackle remaining challenges, we’ve organized expert workshops at the University of Oslo, including one focused on “Addressing the effects of polyploidization and their evolutionary implications”, and another on “Towards sustainable microbial biotechnology, overcoming challenges in the genome editing of industrially relevant yeast”. These collaborations are helping us refine our methods and expand the potential of our yeast toolbox. While we’re not producing food directly, some of our evolved strains may find applications in the brewing industry, especially those that thrive on maltose and low temperatures. But the heart of our work lies in transforming waste into resources, paving the way for a more sustainable future. Yeast may be small, but its potential is enormous. By unlocking its hidden powers, we’re turning yesterday’s waste into tomorrow’s solutions — for energy, health, and the planet.

Polyploidization is a recurrent evolutionary phenomenon that generates diversity and facilitates adaptation. The food production chain requires new industrial strains, more efficient or with innovative solutions to particular problems. Synthetic biology tools can introduce biological parts for improving industrial strains. However, some of those parts are still unknown. Industrially relevant yeasts are polyploids suggesting polyploidization as a mechanism to generate new industrial strains. Allopolyploids can combine multiple parental traits. But, the effects of polyploidization are not well understood. In PloidYeast, we will apply a multidisciplinary approach combining microbiology, molecular and genetic engineering methods, bioinformatics and mathematical modelling to generate a new generation of industrial strains with application in the food production chain and advance in our understanding of adaptation by polyploidization. First, we will ask whether polyploidization mechanism is a suitable mechanism to improve bioprocesses (Q1). We selected wild yeast species (WP1) to generate auto- and allopolyploids (WP2). We will test whether multi-species allopolyploids show multiple traits (Hypothesis: H1). Then, we will evolve the new polyploids on environments mimicking three industrial conditions (WP3) expecting adaptation to them (H2). After 500 generations of evolution, we will ask whether the effects of polyploidization are repeated (Q2) by sequencing the genomes, transcriptomes and quantifying their proteome, metabolome and other phenotypic traits (WP4). If Q2 is true, we will isolate genomic regions relevant to solve a biotechnological challenge (H3). We envision to use this new multiomic dataset to build the bases of a new generation of mathematical models applied to yeast polyploids to select wild strains (H4) and isolate biological parts contributing to solutions for sustainability of food systems and promotion of circular bioeconomy.