Page 137 - 《中国药科大学学报》2026年第1期

第 57 卷第 1 期 陈 青，等：核糖体肽中的环芳基交联 131

下，在两个芳香环之间形成交联 。 crosslinking in RiPP biosynthesis[J]. Nat Chem Biol, 2025,
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RiPP 天然产物中的环芳基交联常发生在惰性
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原子间，并且在化学上往往极具挑战。不断涌现的 ing of previously crystallized pyruvate formate-lyase activating
环芳基交联 RiPP 以其多样性和复杂性展示了生命 enzyme reveals insights into SAM binding and reductive cleav-
体系的巨大合成潜力。尽管 rSAM 酶和 P450 酶 age[J]. J Biol Chem, 2023, 299(6): 104791.
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功能强大的酶有望应用于更多惰性分子的交联，为
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目前环芳基交联 RiPP 的研究仍面临着诸多挑
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战。例如，酶结构与功能关系解析的不足，未来，仍 [11] Grell TAJ, Goldman PJ, Drennan CL. SPASM and twitch do-
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前体肽关键残基的突变研究，深入解析酶结构与功
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芳基交联产物的生物活性方面，虽然 darobactin 和
atypical atropisomerism in a small-molecule natural product,
dynobactin 展示出较强的抗菌活性与独特的作用机 tryptorubin A[J]. Science, 2020, 367(6476): 458-463.
制，但绝大多数环芳基交联 RiPP 的功能和活性尚 [14] Kunakom S, Otani H, Udwary DW, et al. Cytochromes P450 in-
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未得到阐明。未来仍需注重真实产物的获取，如在
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原宿主菌中原位激活 BGC，或在近缘物种中异源表 [15] Nguy AKL, Martinie RJ, Cai A, et al. Detection of a kinetically
达获得成熟产物；同时，还需拓展活性测试范围，包 competent compound-I intermediate in the vancomycin biosyn-
括抗细菌、抗真菌、抗肿瘤、抗病毒、免疫抑制等。 thetic enzyme OxyB[J]. J Am Chem Soc, 2024, 146(29): 19629-
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性，可以期待，随着未来更多该类产物的不断涌现， tural basis of the reaction catalyzed by CYP121, an essential cy-
以及活性和机制研究的逐渐深入，环芳基交联 tochrome P450 in Mycobacterium tuberculosis[J]. Proc Natl
Acad Sci USA, 2009, 106(18): 7426-7431.
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