Seshadri Kaushik, Abad Abner N D, Nagasawa Kyle K, Yost Karl M, Johnson Colin W, Dror Moriel J, Tang Yi
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, 420 Westwood Plaza, Los Angeles, California 90095, United States.
Department of Chemistry and Biochemistry, University of California, Los Angeles, 420 Westwood Plaza, Los Angeles, California 90095, United States.
Chem Rev. 2025 Apr 9;125(7):3814-3931. doi: 10.1021/acs.chemrev.4c00567. Epub 2025 Mar 21.
Synthetic biology has played an important role in the renaissance of natural products research during the post-genomics era. The development and integration of new tools have transformed the workflow of natural product discovery and engineering, generating multidisciplinary interest in the field. In this review, we summarize recent developments in natural product biosynthesis from three different aspects. First, advances in bioinformatics, experimental, and analytical tools to identify natural products associated with predicted biosynthetic gene clusters (BGCs) will be covered. This will be followed by an extensive review on the heterologous expression of natural products in bacterial, fungal and plant organisms. The native host-independent paradigm to natural product identification, pathway characterization, and enzyme discovery is where synthetic biology has played the most prominent role. Lastly, strategies to engineer biosynthetic pathways for structural diversification and complexity generation will be discussed, including recent advances in assembly-line megasynthase engineering, precursor-directed structural modification, and combinatorial biosynthesis.
合成生物学在后基因组时代天然产物研究的复兴中发挥了重要作用。新工具的开发与整合改变了天然产物发现与工程的工作流程，引发了该领域的多学科关注。在本综述中，我们从三个不同方面总结了天然产物生物合成的最新进展。首先，将涵盖用于鉴定与预测生物合成基因簇（BGC）相关的天然产物的生物信息学、实验和分析工具的进展。接下来将广泛综述天然产物在细菌、真菌和植物生物体中的异源表达。天然产物鉴定、途径表征和酶发现的独立于天然宿主的范式是合成生物学发挥最突出作用的领域。最后，将讨论用于结构多样化和复杂性生成的生物合成途径工程策略，包括装配线巨型合成酶工程、前体导向结构修饰和组合生物合成的最新进展。
