天然产物生物合成与微生物制造的挑战

Natural products are a treasure trove given to mankind by nature and are intimately linked to human quality of life and health. Traditional methods of obtaining natural products face challenges such as low natural biocontent, complex and time-consuming extraction processes, and unsustainable resource utilization. The intricate structures of natural products also severely impede the commercialization of chemical total synthesis. Microbial cell factories, empowered by synthetic biology, have the potential to revolutionize the current approaches to natural product extraction, with the goal of efficient, eco-friendly, and controllable biomanufacturing. This review discusses the challenges posed by traditional methods of obtaining natural products and summarizes the characteristics of different types of cell factories along with examples of natural product synthesis. Considering the complexity of natural product metabolic pathways and issues such as unpredictable product structure and properties, low purity, and low yield due to the stability of chassis cells, the article analyzes the challenges in designing microbial cell factories from the perspective of catalytic component limitations, pathway assembly regulation, and chassis cell network remodeling. Strategies and countermeasures are discussed. Moreover, recommendations are proposed to address the current regulatory constraints in microbial manufacturing.