Journal of Energy Bioscience 2025, Vol.16, No.5, 227-237 http://bioscipublisher.com/index.php/jeb 233 increase their sensitivity to chemotherapy and radiotherapy (Jiang et al., 2014; Sarfraz et al., 2020; Ghanem et al., 2021; Wu et al., 2024; Qiao et al., 2025). If PPP inhibitors are used in combination with traditional chemotherapy drugs, a synergistic effect can also be produced, inducing oxidative stress and apoptosis of tumor cells (Liu et al., 2020; Kaushik et al., 2021; Meskers et al., 2022). However, at present, PPP inhibitors still face many challenges in terms of toxicity, specificity and clinical application. In the future, safer and more effective targeted drugs need to be developed. 8 Biotechnological and Clinical Applications 8.1 Metabolic engineering The pentose phosphate pathway (PPP) is a common modification target in metabolic engineering and is widely used in the industrial production of microorganisms and fungi. By regulating the expression of PPP-related enzymes, the supply of NADPH can be significantly increased, thereby enhancing the synthesis efficiency of various high-value products, such as polyols, biofuels, carotenoids and antibiotics, etc. In some industrial fungi, engineered PPP modification has been proven to increase yield, optimize carbon flow distribution, and enable cells to better adapt to different carbon sources and oxidative stress conditions (Bertels et al., 2021; Masi et al., 2021). In addition, computational models based on cohort theory have also been used to simulate the metabolic flow of PPP, providing new tools for drug development, which can accelerate the screening of new drugs and reduce the use of animal experiments (Kloska et al., 2022). 8.2 Therapeutics PPP is a potential therapeutic target in a variety of diseases, especially cancer. Cancer cells usually up-regulate PPP to meet the demands of rapid proliferation and antioxidation. If the key enzymes of PPP (such as G6PD, 6PGD, TKT) are inhibited, the proliferation ability, drug resistance and resistance to radiotherapy or chemotherapy of cancer cells can be reduced (Rahman and Hasan, 2014; Cho et al., 2017; Ghanem et al., 2021; Polat et al., 2021; Qiao et al., 2025). The combined use of PPP inhibitors and traditional anti-cancer drugs (such as cisplatin) can also enhance the therapeutic effect. At present, some drug delivery systems have also been able to achieve targeting on tumor cells (Giacomini et al., 2020; Shimoni-Sebag et al., 2024). Furthermore, regulating PPP has also been studied for improving the efficacy of immunotherapy, enhancing antioxidant defense, and treating hemolytic diseases (Bories et al., 2020; TeSlaa et al., 2023; Markowitz et al., 2024). 8.3 Diagnostics The changes in PPP activity also bring new methods for disease diagnosis and therapeutic effect monitoring. Metabolic imaging techniques (such as magnetic resonance spectroscopy MRS) can detect glucose entry into PPP, thereby enabling non-invasive monitoring of TERT expression and metabolic reprogramming in tumors (such as low-grade gliomas) (Viswanath et al., 2021). Furthermore, detecting the activity of PPP-related enzymes (such as G6PD) is helpful for determining hereditary hemolytic anemia, tumor subtypes, and drug sensitivity (Polat et al., 2021; Tang et al., 2023; TeSlaa et al., 2023). Metabolomics and systems biology methods have also shown application potential in early disease screening and individualized treatment (Rashida and Laxman, 2021). 9 Future Directions 9.1 Systems biology approaches Systems biology provides a powerful tool for understanding the role of the pentose phosphate pathway (PPP) in cellular metabolism. In recent years, researchers have revealed the connections between PPP and multiple pathways such as amino acids and lipids by combining omics data, metabolic flow analysis and network modeling, and have also observed its overall role in cell growth, stress and synthesis processes (Bertels et al., 2021; Rashida and Laxman, 2021). For instance, computational models such as queue theory have been employed to simulate the changes in the concentration of PPP metabolites and verify their stability in complex environments like tumor cells. These results also provide a theoretical basis for drug development and metabolic engineering (Kloska et al., 2022). In the future, systems biology will continue to help us understand the overall regulatory mechanisms of PPP in different physiological and pathological states.
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