Deparment of Chemistry and Biochemistry, University of California, Santa Cruz, 1156 High Street, Santa Cruz, California 95064, United States.
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390 United States.
Chem Rev. 2022 Sep 28;122(18):14815-14841. doi: 10.1021/acs.chemrev.2c00306. Epub 2022 Aug 25.
Biosynthetic mechanisms of natural products primarily depend on systems of protein catalysts. However, within the field of biosynthesis, there are cases in which the inherent chemical reactivity of metabolic intermediates and substrates evades the involvement of enzymes. These reactions are difficult to characterize based on their reactivity and occlusion within the milieu of the cellular environment. As we continue to build a strong foundation for how microbes and higher organisms produce natural products, therein lies a need for understanding how protein independent or nonenzymatic biosynthetic steps can occur. We have classified such reactions into four categories: intramolecular, multicomponent, tailoring, and light-induced reactions. Intramolecular reactions is one of the most well studied in the context of biomimetic synthesis, consisting of cyclizations and cycloadditions due to the innate reactivity of the intermediates. There are two subclasses that make up multicomponent reactions, one being homologous multicomponent reactions which results in dimeric and pseudodimeric natural products, and the other being heterologous multicomponent reactions, where two or more precursors from independent biosynthetic pathways undergo a variety of reactions to produce the mature natural product. The third type of reaction discussed are tailoring reactions, where postmodifications occur on the natural products after the biosynthetic machinery is completed. The last category consists of light-induced reactions involving ecologically relevant UV light rather than high intensity UV irradiation that is traditionally used in synthetic chemistry. This review will cover recent nonenzymatic biosynthetic mechanisms and include sources for those reviewed previously.
天然产物的生物合成机制主要依赖于蛋白质催化剂系统。然而，在生物合成领域，存在代谢中间体和底物的固有化学反应性逃避酶参与的情况。这些反应基于其反应性和在细胞环境中的掩蔽性很难进行特征描述。随着我们继续为微生物和高等生物生产天然产物建立坚实的基础，就需要了解非蛋白依赖或非酶生物合成步骤如何发生。我们将这些反应分为四类：分子内、多组分、修饰和光诱导反应。分子内反应是生物模拟合成中研究最多的反应之一，由于中间体的固有反应性，包括环化和环加成反应。多组分反应有两个子类，同源多组分反应导致二聚体和拟二聚体天然产物，而异源多组分反应则是两个或多个来自独立生物合成途径的前体经历各种反应以产生成熟的天然产物。讨论的第三种反应是修饰反应，其中在生物合成机制完成后对天然产物进行后修饰。最后一类是光诱导反应，涉及生态相关的紫外光，而不是传统合成化学中使用的高强度紫外光。本综述将涵盖最近的非酶生物合成机制，并包括以前综述过的来源。
