Lessons learned from the transformation of natural product discovery to a genome-driven endeavor

Caitlin D. Deane, Douglas A. Mitchell

Research output: Contribution to journalReview articlepeer-review


Natural product discovery is currently undergoing a transformation from a phenotype-driven field to a genotype-driven one. The increasing availability of genome sequences, coupled with improved techniques for identifying biosynthetic gene clusters, has revealed that secondary metabolomes are strikingly vaster than previously thought. New approaches to correlate biosynthetic gene clusters with the compounds they produce have facilitated the production and isolation of a rapidly growing collection of what we refer to as "reverse- discovered" natural products, in analogy to reverse genetics. In this review, we present an extensive list of reverse-discovered natural products and discuss seven important lessons for natural product discovery by genome-guided methods: structure prediction, accurate annotation, continued study of model organisms, avoiding genome-size bias, genetic manipulation, heterologous expression, and potential engineering of natural product analogs.

Original languageEnglish (US)
Pages (from-to)315-331
Number of pages17
JournalJournal of Industrial Microbiology and Biotechnology
Issue number2
StatePublished - Feb 2014


  • Biosynthetic gene clusters
  • Genetic manipulation
  • Genome mining
  • Heterologous expression
  • Natural products
  • Reverse discovery
  • Structure prediction

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology


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