Progress in combinatorial biosynthesis for drug discovery

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14 Scopus citations

Abstract

Combinatorial biosynthesis, the process of genetic manipulations of natural product biosynthetic machinery for structural diversity, depends on several factors, and discussed here are two critical factors: access to genetic information and biochemical characterization of enzymes. Examples of the former include using predictions for the biosynthesis of unusual chemical entities such as aminohydroxybenzoic acid starter units, methoxymalonylate extender units, the enediyne core and bacterial aromatic polyketides. The latter aspect includes the continued elucidation of domain functionalities of modular polyketide synthases and nonribosomal peptide synthases and novel biochemical pathways such as the biosynthesis of a cyclopropyl unit and a β-hydroxyl acid. Finally, examples of successful combinatorial biosynthesis for daptomycin and indolocarbozole compounds are discussed.

Original languageEnglish
Pages (from-to)285-292
Number of pages8
JournalDrug Discovery Today: Technologies
Volume3
Issue number3
DOIs
StatePublished - Sep 2006

Bibliographical note

Funding Information:
Current studies on natural product biosynthesis and engineering described from the Shen laboratory are supported in part by National Institutes of Health (NIH) grants CA94426, CA78747, CA106150, and CA113296. S.V.L is a recipient of an NIH postdoctoral fellowship CA1059845, and B.S is the recipient of an NIH Independent Scientist Award AI51689.

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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