Pharmaceutically active natural product synthesis and supply via plant cell culture technology

The chemical diversity of plant-derived natural products allows them to function in a multitude of ways including flavor enhancers, agricultural chemicals, and importantly, human medicinals. Supply of pharmaceutically active natural products is often a challenge due to the slow growing nature of some species, low yields found in nature, and unpredictable variability in accumulation. Several production options are available including natural harvestation, total chemical synthesis, semisynthesis from isolated precursors, and expression of plant pathways in microbial systems. However, for some medicinal natural products, such as the anticancer agent paclitaxel, where low yields in nature, chemical complexity and lack of knowledge of the complete biosynthetic pathway, preclude many of these options, plant cell culture technology is an attractive alternative for supply. Plant cell suspension cultures are amenable to scale-up, environmental optimization, and metabolic engineering. This review focuses on some of the key challenges in utilizing and commercializing plant cell culture suspension technology, with a focus on pharmaceutically active natural products. Recent research has been directed toward application of traditional strategies such as reactor design, cell immobilization, and enzyme elicitation as well as emerging strategies such as characterizing cellular heterogeneity and variability through flow cytometric techniques, metabolic engineering, and system-wide analysis.