Advancing stress biotechnology for robust sustainable bioproduction

Environmental stressors compromise the economic viability of microbial bioproduction, making enhanced microbial robustness essential. While traditional engineering strategies try to maximize cell growth and survival, recent studies reveal that there exists a proper balance between stress tolerance and bioproduction efficiency. Here, we propose the concept of stress biotechnology and summarize relevant advances in yeast research, particularly focusing on global metabolic rewiring, cell lifespan engineering, and artificial membrane-less organelles. Unlike conventional stress biology focusing mainly on stress tolerance mechanisms, stress biotechnology precisely partitions resources to achieve a delicate balance between cellular defense and product synthesis. The integration of rational and random strategies is emphasized, highlighting major random strategies such as adaptive laboratory evolution and CRISPR interference library approaches. Finally, we discuss future perspectives on leveraging artificial intelligence to identify novel stress-tolerance targets and engineer autonomous dynamic circuits. This review provides a foundation for building next-generation intelligent and robust yeast cell factories.