Journal of Industrial Microbiology & Biotechnology

, Volume 41, Issue 2, pp 315–331

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



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.


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


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Copyright information

© Society for Industrial Microbiology and Biotechnology 2013

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Institute for Genomic BiologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  3. 3.Department of MicrobiologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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