Suresh Amarthya, Vaithilingam Mohanasrinivasan
School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, 632014, Tamil Nadu, India.
Arch Microbiol. 2025 Aug 19;207(9):229. doi: 10.1007/s00203-025-04409-w.
Inflammation is the body's natural defence response to pathogens or tissue injury. This review explores the therapeutic potential of microbial proteases in managing inflammation, focusing on their molecular mechanisms, production strategies, and emerging role as alternatives to conventional anti-inflammatory drugs. While standard treatments such as Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and glucocorticoids act by inhibiting cyclooxygenase enzymes and prostaglandin synthesis, their prolonged use is often associated with adverse effects, including gastrointestinal ulcers, renal toxicity, and cardiovascular complications. Microbial proteases, by contrast, offer advantages such as catalytic specificity, biochemical diversity, and ease of large-scale production through fermentation and genetic modification. In addition to examining market trends of the currently available enzyme-based therapies, this review highlights several key considerations limiting their clinical adoption-namely, immune system sensitivity, poor stability under physiological conditions, limited comparative performance data against other enzyme sources, and challenges in regulatory approval and targeted delivery. It also uniquely highlights underexplored bacterial genera and production challenges, offering a translational outlook that bridges laboratory findings with real-world therapeutic applications. Advances in strain engineering, encapsulation techniques, and synthetic biology approaches hold promise for enhancing the safety, effectiveness, and precision of microbial protease-based therapeutics in inflammation control.
炎症是机体对病原体或组织损伤的自然防御反应。本综述探讨了微生物蛋白酶在炎症治疗中的潜在应用，重点关注其分子机制、生产策略以及作为传统抗炎药物替代品的新兴作用。虽然非甾体抗炎药（NSAIDs）和糖皮质激素等标准治疗方法通过抑制环氧化酶和前列腺素合成发挥作用，但其长期使用往往会带来不良反应，包括胃肠道溃疡、肾毒性和心血管并发症。相比之下，微生物蛋白酶具有催化特异性、生化多样性以及通过发酵和基因改造易于大规模生产等优点。除了研究当前基于酶的疗法的市场趋势外，本综述还强调了限制其临床应用的几个关键因素，即免疫系统敏感性、生理条件下稳定性差、与其他酶源相比性能数据有限以及监管批准和靶向递送方面的挑战。它还特别强调了未充分探索的细菌属和生产挑战，提供了一个将实验室研究结果与实际治疗应用联系起来的转化前景。菌株工程、封装技术和合成生物学方法的进展有望提高基于微生物蛋白酶的疗法在炎症控制中的安全性、有效性和精准性。
