CAS Key Laboratory of Biofuels, Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, 189 Songling Road, Qingdao 266101, China.
Shandong Energy Institute, 189 Songling Road, Qingdao 266101, China.
Molecules. 2023 Aug 3;28(15):5850. doi: 10.3390/molecules28155850.
Enzymes are essential catalysts for various chemical reactions in biological systems and often rely on metal ions or cofactors to stabilize their structure or perform functions. Improving enzyme performance has always been an important direction of protein engineering. In recent years, various artificial small molecules have been successfully used in enzyme engineering. The types of enzymatic reactions and metabolic pathways in cells can be expanded by the incorporation of these artificial small molecules either as cofactors or as building blocks of proteins and nucleic acids, which greatly promotes the development and application of biotechnology. In this review, we summarized research on artificial small molecules including biological metal cluster mimics, coenzyme analogs (mNADs), designer cofactors, non-natural nucleotides (XNAs), and non-natural amino acids (nnAAs), focusing on their design, synthesis, and applications as well as the current challenges in synthetic biology.
酶是生物系统中各种化学反应的重要催化剂，通常依赖金属离子或辅因子来稳定其结构或发挥功能。提高酶的性能一直是蛋白质工程的重要方向。近年来，各种人工小分子已成功应用于酶工程。通过将这些人工小分子作为辅因子或作为蛋白质和核酸的构建块掺入，可以扩展细胞中酶促反应和代谢途径，极大地促进了生物技术的发展和应用。在这篇综述中，我们总结了人工小分子的研究，包括生物金属簇模拟物、辅酶类似物（mNADs）、设计辅因子、非天然核苷酸（XNAs）和非天然氨基酸（nnAAs），重点介绍了它们的设计、合成和应用以及合成生物学中的当前挑战。
