Target-Directed Evolution of Mutant Transgenic Plant Cells as a Novel Source of Drugs

John Littleton, Dustin Brown, Deane Falcone, Gregory Gerhardt, Samir Gunjan, Dennis T. Rogers, Jatinder Sambi

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


Most current non-peptide drugs are derived from bioactive metabolites in wild-type plants. These have mostly evolved in plant species, by mutation and natural selection over millennia, because they confer a survival advantage. A novel approach is to first transform plant cells to express a specific foreign therapeutic target protein, and then derive a mutant population of these transgenic cells by selection under conditions in which metabolites with the desired interaction with the foreign target protein confer a survival advantage. The surviving sub-population of mutants is now enriched in individual clones that overproduce known or novel metabolites with the required activity on the target. Within months, "target-directed evolution" can redirect the "bioactive metabolome" of the plant species toward a specific pharmacological phenotype. In this chapter we describe how this approach constitutes a powerful means of evolving plant secondary metabolism thus enhancing the natural capability of plant cells.

Original languageEnglish
Title of host publicationMolecular Pharming
Subtitle of host publicationApplications, Challenges and Emerging Areas
Number of pages22
ISBN (Electronic)9781118801512
StatePublished - Sep 12 2018

Bibliographical note

Publisher Copyright:
© 2018 John Wiley & Sons, Inc.


  • Biosynthesis
  • Metabolite
  • Mutation
  • Pharmaceutical
  • Selection
  • Transporter protein

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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