Journal of Energy Bioscience 2025, Vol.16, No.5, 227-237 http://bioscipublisher.com/index.php/jeb 234 9.2 Emerging technologies Some new technologies are accelerating the research on PPP. High-throughput gene editing (such as CRISPR screening), metabolomics, single-cell analysis and real-time metabolic imaging have all been used to discover the regulatory factors of PPP and its unconventional roles in oxidative stress and tumor metabolism (Dubreuil et al., 2020; Masi et al., 2021). In addition, synthetic biology methods such as automated carbon flow redirection and oxygen-responsive metabolic switches have also achieved precise regulation of PPP in microorganisms and fungi. These methods can significantly increase NADPH supply and the yield of the target product (Kobayashi et al., 2020). These technologies have brought new opportunities for metabolic engineering, disease treatment and biomanufacturing. 9.3 Open questions Although significant progress has been made in the research of PPP, there are still many unknowns. First of all, the regulatory network of PPP is very complex and is not yet fully understood. Further research is needed on how signals such as carbon sources, nitrogen sources and oxidative stress jointly regulate PPP and its transcription factors (Masi et al., 2021; Rashida and Laxman, 2021). Secondly, the dynamic regulatory patterns of PPP in different cell types, developmental stages and disease states, as well as its relationship with other metabolic pathways, are not yet clear (Bertels et al., 2025). In addition, the sensitivity of PPP key enzymes to oxidative damage and their fine regulatory mechanisms in antioxidant defense also require more in-depth molecular-level studies (Fuentes-Lemus et al., 2023). Finally, how to combine systems biology with emerging technologies to achieve precise regulation and individualized intervention of PPP is an important issue to be solved in the future. 10 Conclusion The pentose phosphate pathway (PPP) is an important branch in cellular metabolism, which is related not only to energy metabolism but also to biosynthesis. PPP has two parts. Oxidative branches generate NADPH, which can provide reducing power for the synthesis of fatty acids, cholesterol and other substances, and also maintain the REDOX balance of cells, helping to resist oxidative stress. The non-oxidizing branch provides substances such as ribose 5-phosphate, which are used to synthesize nucleotides and amino acids. This flexibility makes PPP important in cell proliferation, differentiation and immune defense, and also plays a key role when cells are under oxidative stress. In a healthy state, PPP can support cell growth, assist in antioxidant defense, and also ensure the replication of genetic material. However, in some diseases, such as G6PD deficiency, diabetes or tumors, the regulation of PPP may encounter problems. It either weakens its function or becomes overly active, thereby affecting the survival, proliferation and response of cells to drugs. Especially in tumors, cells enhance the activity of PPP to meet the needs of rapid synthesis and antioxidation, which also makes PPP a new target for anti-cancer treatment. Meanwhile, PPP also has great value in biotechnology. Regulating PPP through metabolic engineering can enhance the product synthesis efficiency of industrial microorganisms and promote the development of biomanufacturing and green industries. Although the role of PPP has been widely recognized, its regulatory network is very complex. How PPP is interrelated with other metabolic pathways and how it changes in different cell types and disease states remain to be studied. In the future, if systems biology can be combined with emerging technologies, it is expected to achieve precise regulation of PPP. This can not only promote the progress of disease treatment, but also facilitate industrial applications. Continuous and in-depth research on PPP will provide a solid foundation for the development of new treatment methods and efficient biomanufacturing platforms. Acknowledgments We would like to express our gratitude to the two anonymous peer researchers for their constructive suggestions on our manuscript. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.
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