Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, and Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China; State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, and Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China; Hubei Engineering Laboratory for Synthetic Microbiology, Wuhan Institute of Biotechnology, Wuhan 430075, China.
Metab Eng. 2017 Jan;39:228-236. doi: 10.1016/j.ymben.2016.12.006. Epub 2016 Dec 21.
Natural products (NPs) and their derivatives are widely used as frontline treatments for many diseases. Actinobacteria spp. are used to produce most of NP antibiotics and have also been intensively investigated for NP production, derivatization, and discovery. However, due to the complicated transcriptional and metabolic regulation of NP biosynthesis in Actinobacteria, especially in the cases of genome mining and heterologous expression, it is often difficult to rationally and systematically engineer synthetic pathways to maximize biosynthetic efficiency. With the emergence of new tools and methods in metabolic engineering, the synthetic pathways of many chemicals, such as fatty acids and biofuels, in model organisms (e.g. Escherichia coli ), have been refactored to realize precise and flexible control of production. These studies also offer a promising approach for synthetic pathway refactoring in Actinobacteria. In this review, the great potential of Actinobacteria as a microbial cell factory for biosynthesis of NPs is discussed. To this end, recent progress in metabolic engineering of NP synthetic pathways in Actinobacteria are summarized and strategies and perspectives to rationally and systematically refactor synthetic pathways in Actinobacteria are highlighted.
天然产物 (NPs) 及其衍生物被广泛用作许多疾病的一线治疗方法。放线菌被用于生产大多数 NP 抗生素，并且也被广泛用于 NP 的生产、衍生化和发现研究。然而，由于 NP 生物合成在放线菌中的转录和代谢调控非常复杂，特别是在基因组挖掘和异源表达的情况下，通常很难合理且系统地工程化合成途径以最大化生物合成效率。随着代谢工程中新型工具和方法的出现，许多化学物质（如脂肪酸和生物燃料）的合成途径已在模式生物（如大肠杆菌）中进行了重构，以实现生产的精确和灵活控制。这些研究也为放线菌中的合成途径重构提供了有前途的方法。在本文中，讨论了放线菌作为 NP 生物合成的微生物细胞工厂的巨大潜力。为此，总结了放线菌中 NP 合成途径代谢工程的最新进展，并强调了合理且系统地重构放线菌中合成途径的策略和观点。
