Issatchenkia orientalis as a platform organism for cost-effective production of organic acids

Driven by the urgent need to reduce the reliance on fossil fuels and mitigate environmental impacts, microbial cell factories capable of producing value-added products from renewable resources have gained significant attention over the past few decades. Notably, non-model yeasts with unique physiological characteristics have emerged as promising candidates for industrial applications, particularly for the production of organic acids. Among them, Issatchenkia orientalis stands out for its exceptional natural tolerance to low pH and high osmotic pressure, traits that are critical for overcoming the limitations of conventional microbial organisms. The acid tolerance of I. orientalis enables organic acid production under low pH conditions, bypassing the need for expensive neutral pH control typically required in conventional processes. Organic acids produced by I. orientalis, such as lactic acid, succinic acid, and itaconic acid, are widely used as building blocks for bioplastics, food additives, and pharmaceuticals. This review summarizes the key findings from systems biology studies on I. orientalis over the past two decades, providing insights into its unique metabolic and physiological traits. Advances in genetic tool development for this non-model yeast are also discussed, enabling targeted metabolic engineering to enhance its production capabilities. Additionally, case studies are highlighted to illustrate the potential of I. orientalis as a platform organism. Finally, the remaining challenges and future directions are addressed to further develop I. orientalis into a robust and versatile microbial cell factory for sustainable biomanufacturing.