Reconstruction of genome-scale metabolic models of non-conventional yeasts: current state, challenges, and perspectives

Non-conventional yeasts are promising cell factories to produce lipids and oleochemicals, metabolites of industrial interest (e.g., organics acids, esters, and alcohols), and enzymes. They can also use different agro-industrial by-products as substrates within the context of a circular economy. Some of these yeasts can also comprise economic and health burdens as pathogens. Genome-scale metabolic models (GEMs), networks reconstructed based on the genomic and metabolic information of one or more organisms, are great tools to understand metabolic functions and landscapes, as well as propose engineering targets to improve metabolite production or propose novel drug targets. Previous reviews on yeast GEMs have mainly focused on the history and the evaluation of Saccharomyces cerevisiae modeling paradigms or the accessibility and usability of yeast GEMs. However, they did not describe the reconstruction strategies, limitations, validations, challenges, and research gaps of non-conventional yeast GEMs. Herein, we focused on the reconstruction of available non-Saccharomyces GEMs, their validation, underscoring the physiological insights, as well as the identification of both metabolic engineering and drug targets. We also discuss the challenges and knowledge gaps and propose strategies to boost their use and novel reconstructions.