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Diversifying carotenoid biosynthetic pathways by directed evolution.

Daisuke Umeno1, Alexander V Tobias, Frances H Arnold

  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, 210-41, 1200 E. California Blvd., Pasadena, CA 91125, USA.

Microbiology and Molecular Biology Reviews : MMBR
|March 10, 2005
PubMed
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Researchers are using laboratory evolution to create novel natural products. By evolving biosynthetic pathways, they have discovered new carotenoids with unique structures not found in nature.

Area of Science:

  • Biotechnology
  • Natural Product Discovery
  • Synthetic Biology

Background:

  • Microorganisms and plants produce numerous natural products vital for human health.
  • The vast majority of potential natural products remain undiscovered.
  • Chemical synthesis and recombinant organisms have expanded natural product diversity.

Purpose of the Study:

  • To explore the potential of laboratory evolution for discovering new natural products.
  • To detail methods for generating novel biosynthetic pathways.
  • To discuss the application of these methods to other natural product classes.

Main Methods:

  • Applying evolution-inspired methods to biosynthetic pathways in laboratory organisms.
  • Engineering carotenoid biosynthetic pathways by mixing, matching, and mutating enzymes.

Related Experiment Videos

  • Screening libraries of evolved pathways for novel product formation.

    • Main Results:

    • Generated dozens of new carotenoid products previously unknown.
    • Created novel carotenoid families with non-natural backbones.
    • Demonstrated the utility of laboratory evolution for pathway engineering.

    Conclusions:

    • Laboratory evolution is a powerful strategy for discovering novel natural products.
    • This approach significantly expands the accessible chemical space of natural products.
    • The methods discussed have broad applicability to other biosynthetic pathways.