Natural Products Genomics: A novel approach for the discovery of anti-cancer therapeutics

作者：Monks N R^*; Li B; Gunjan S; Rogers D T; Kulshrestha M; Falcone D L; Littleton J M

来源：Journal of Pharmacological and Toxicological Methods, 2011, 64(3): 217-225.

DOI：10.1016/j.vascn.2011.04.002

• Natural Products Genomics
• Activation Tagging Mutagenesis
• Directed evolution
• Directed elicitation
• Vinca alkaloids
• High-Throughput Differential Screening

Plants continue to retain some advantages over combinatorial chemistry as sources of novel compounds, for example, they can generate metabolites with a complexity beyond synthetic chemistry. However, this comes with its own problems in production and synthetic modification of these compounds. Natural Products Genomics (NPG) aims to access the plants own genomic capacity to increase yields, and modify complex bioactive metabolites, to alleviate these limitations. NPG uses a combination of gain of function mutagenesis and selection to a) mimic the evolution of novel compounds in plants, and b) to increase yields of known bioactive metabolites. This process is performed rapidly at the cell culture level in large populations of mutants. Two examples demonstrating proof of concept in Nicotiana tabacum (tobacco) and proof of application in the medicinal plant species Catharanthus roseus, are included to illustrate the feasibility of this approach. This biotechnology platform may alter the way in which plant drug discovery is perceived by the pharmaceutical industry, and provides an alternative to combinatorial chemistry for the discovery, modification and production of highly complex bioactive molecules.

• 出版日期2011-12