Terpene cyclases (TCs) are pivotal enzymes in nature, orchestrating the intricate synthesis of terpenes, a diverse group of natural compounds with profound biological activities. This review delves into the multifaceted roles of terpene cyclases, which serve as nature’s biochemical architects, sculpting the chemical landscape of plants, fungi, and bacteria. Understanding the catalytic mechanisms of TCs unveils the astounding diversity of terpenes and their vital functions in plant defense, pollination, and growth regulation. Moreover, this review examines the classification of TCs, shedding light on their distinct classes and the array of terpenoids they produce, each with unique biological activities. Exploration of terpenes in cancer therapy uncovers their promising anti-cancer properties, targeting key hallmarks of cancer progression such as proliferation, survival, and metastasis. This review elaborates on various mechanisms through which terpenes induce apoptosis, inhibit tumor growth, modulate immune responses, and enhance chemotherapy efficacy. Additionally, it includes case studies and ongoing clinical trials showcasing the efficacy of terpene-based treatments across different cancer types. Challenges in utilizing terpenes for cancer therapy, such as stability, specificity, and drug resistance, are outlined, alongside strategies to overcome these hurdles. A significant highlight of this review is the potential of engineered terpene cyclases for tailored therapies. Directed evolution and rational enzyme design strategies offer avenues to create designer terpenes optimized for anti-cancer properties. This review culminates in a comprehensive exploration of synergistic approaches, combining terpenes with chemotherapy, immunotherapy, and targeted therapies to enhance treatment efficacy and minimize side effects. Through the lens of terpene cyclases, it provides a broad overview of the diverse landscape of terpenes in nature, their potential in cancer therapy, and the exciting frontier of engineered terpene-based therapies.
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