Advances in the Biosynthetic Production of Daunomycin: Genetic, Metabolic, and Process Engineering Strategies

Daunomycin (daunorubicin) is one of the most clinically significant anthracyclines used in chemotherapy, and its efficient production remains a major objective for biotechnological researchers. Industrial manufacturing relies on the fermentation of Streptomyces peucetius and Streptomyces coeruleorubidus, which produce daunomycin as a secondary metabolite under controlled conditions. This review will focus on the methods to enhance the total efficiency of biotechnological production, from upstream biosynthesis to downstream processing. Given the complexity of the daunomycin biosynthetic pathway in Streptomyces spp., substantial progress has been made in strain improvement to increase yield, metabolic robustness, and process stability. Advances in classical mutagenesis, pathway engineering, regulatory network modulation, and precursor supply optimization, along with rational medium design and advanced process control, have led to substantial increases in product titers and productivity. At the same time, innovations in downstream processes, such as extraction, purification and process integration, have increased recovery efficiency, product quality, and economic feasibility. With improvements in the production process, novel drug delivery modalities have been developed (e.g., drug carriers based on erythrocytes, drug nanocarriers based on hyaluronic acid) with increased efficiency and lower systemic toxicity. These developments indicate an evolution from pathway-level engineering to industrial-scale manufacturing and clinical application, underlining the evolution of daunomycin research and biotechnological production.