DNA assembly techniques for next-generation combinatorial biosynthesis of natural products

Ryan E. Cobb, Jonathan C. Ning, Huimin Zhao

Research output: Contribution to journalReview articlepeer-review


Natural product scaffolds remain important leads for pharmaceutical development. However, transforming a natural product into a drug entity often requires derivatization to enhance the compound's therapeutic properties. A powerful method by which to perform this derivatization is combinatorial biosynthesis, the manipulation of the genes in the corresponding pathway to divert synthesis towards novel derivatives. While these manipulations have traditionally been carried out via restriction digestion/ligation-based cloning, the shortcomings of such techniques limit their throughput and thus the scope of corresponding combinatorial biosynthesis experiments. In the burgeoning field of synthetic biology, the demand for facile DNA assembly techniques has promoted the development of a host of novel DNA assembly strategies. Here we describe the advantages of these recently developed tools for rapid, efficient synthesis of large DNA constructs. We also discuss their potential to facilitate the simultaneous assembly of complete libraries of natural product biosynthetic pathways, ushering in the next generation of combinatorial biosynthesis.

Original languageEnglish (US)
Pages (from-to)469-477
Number of pages9
JournalJournal of Industrial Microbiology and Biotechnology
Issue number2
StatePublished - Feb 2014


  • Combinatorial biosynthesis
  • DNA assembly
  • Genome mining
  • Synthetic biology

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology


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