Harnessing Genomic Instability with Al-Driven Adaptive Laboratory Evolution for Accelerated Yeast Bioproduction

The production of high-volume albumins, essential proteins for therapeutics and sustainable food, faces critical bottlenecks. In medicine, the supply of human serum albumin (HSA) is constrained by a reliance on plasma, which carries pathogen risks and supply vulnerabilities. In the food sector, ovalbumin production via precision fermentation offers a sustainable alternative to animal agriculture. Still, they both require overcoming major yield and cost-effectiveness barriers to be viable at an industrial scale. To address these challenges, AI-EvoYeast will exploit the inherent instability of polyploid yeast as an engine for accelerated evolution, integrating it with product-coupled selection to drive the evolution of albumin-hyperproducing strains. By employing an unbiased evolutionary approach, the platform enables the cell itself to explore a vast solution space of mutations, gene expression changes, and network-level adaptations, overcoming the stress of protein hyperproduction and the limits of rational design. The AI-EvoYeast project will develop a next-generation yeast (S. cerevisiae) platform, transforming a biological challenge, genomic instability, into a powerful engineering asset. Unlike traditional Adaptive Laboratory Evolution (ALE), AI-EvoYeast integrates Artificial Intelligence (AI) and Machine Learning (ML), fuelled by multi-omics data, to decipher adaptive mechanisms and build a predictive model for optimal genomic configurations. Insights from explainable AI (XAI) will then guide precise CRISPR interventions to reconstruct superior phenotypes in a stable industrial chassis. This project pioneers a highly generalisable AI-augmented evolutionary strategy. By creating a predictive platform technology estimated to slash R&D timelines by up to 50%, it will secure a sustainable, cost-effective European supply of vital proteins for the pharmaceutical and food industries. This directly supports EU strategic autonomy and leadership in the global bioeconomy.