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Combinatorial biosynthesis for drug development.

Hugo G Menzella1, Christopher D Reeves

  • 1Kosan Biosciences, Inc. 3832 Bay Center Place, Hayward, CA 94545, USA.

Current Opinion in Microbiology
|June 8, 2007
PubMed
Summary
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Combinatorial biosynthesis uses genetic engineering to create novel molecules and compound libraries for drug discovery. This review highlights multi-modular enzymes for producing polyketides and peptides, accelerating new therapeutic development.

Area of Science:

  • Biotechnology
  • Medicinal Chemistry
  • Synthetic Biology

Background:

  • Combinatorial biosynthesis enables genetic engineering of natural product biosynthesis pathways.
  • This approach facilitates the creation of diverse molecular libraries for drug discovery.
  • Multi-modular enzymes, including those for polyketides and nonribosomal peptides, are key targets.

Purpose of the Study:

  • To review the application of combinatorial biosynthesis for generating novel compounds.
  • To focus on multi-modular enzymes amenable to combinatorial strategies.
  • To highlight advancements in high-throughput screening for engineered enzymes.

Main Methods:

  • Review of literature on combinatorial biosynthesis strategies.
  • Focus on genetic engineering of polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS).

Related Experiment Videos

  • Discussion of high-throughput screening methods for assessing combinatorial enzyme libraries.

    • Main Results:

    • Multi-modular enzymes are highly suitable for combinatorial biosynthesis.
    • Engineering these enzymes allows for the production of novel polyketide, nonribosomal peptide, and hybrid compounds.
    • Development of high-throughput strategies is crucial for testing new enzyme combinations.

    Conclusions:

    • Combinatorial biosynthesis offers a powerful route to novel natural products and drug candidates.
    • Multi-modular enzymes represent a promising platform for generating molecular diversity.
    • Advancements in high-throughput testing will accelerate the field of combinatorial biosynthesis.