Rapamycin: From Microbial Discovery to Therapeutic Innovations — Advances, Challenges, and Future Prospects
Keywords:
rapamycin, mTOR signalling, Streptomyces, Rapalogs, pharmacology, biotechnologyAbstract
Background: Rapamycin (sirolimus), originally isolated from Streptomyces hygroscopicus, is a macrolide compound that has profoundly influenced modern biomedical research through its inhibition of the mechanistic target of rapamycin (mTOR) pathway.
Objective: This review aims to synthesize current knowledge on the microbiological origin, molecular mechanisms, therapeutic applications, and biotechnological optimization of rapamycin, with emphasis on recent advances and emerging challenges.
Methods: A comprehensive literature analysis was conducted using peer-reviewed articles focusing on rapamycin biosynthesis, mTOR signaling, clinical applications, and production strategies.
Results: Rapamycin and its analogs (rapalogs) demonstrate significant clinical value in transplantation, oncology, neurodegenerative diseases, and aging research. Advances in metabolic engineering, synthetic biology, and nanodelivery systems have substantially improved production yields and pharmacological performance. However, limitations related to solubility, bioavailability, metabolic side effects, and long-term safety remain.
Conclusion: Rapamycin remains a cornerstone molecule linking microbial natural products to translational medicine. Continued optimization of its production and selective modulation of mTOR signaling are critical for expanding its future therapeutic potential.
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