Enzyme evolution in natural products biosynthesis: target- or diversity-oriented?

Lianet Noda-Garcia, Dan S. Tawfik*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations


Natural product biosynthesis (NPB) is the Panda's Thumb of evolutionary biochemistry. Arm races between organisms, and ever-changing environments, result in relentless innovation. This review focusses on enzyme evolution in NPB. First, we review cases of de novo emergence, whereby a completely new enzymatic activity arose in a ligand-binding protein, or a new enzyme emerged including a completely new scaffold. Second, we briefly review the current models for enzyme evolution, and how they explain the inherent promiscuity of NPB enzymes and their tendency to produce multiple related products. We thus suggest that NPB enzymes a priori evolved to generate a specific product; they are, however, trapped in a multifunctional, generalist evolutionary state and thereby produce a diversity of products.

Original languageAmerican English
Pages (from-to)147-154
Number of pages8
JournalCurrent Opinion in Chemical Biology
StatePublished - Dec 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Ltd


  • Chemical diversity
  • Enzyme evolution
  • Generalist
  • Natural products biosynthesis
  • Promiscuity


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