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

Lianet Noda-Garcia1, Dan S Tawfik2

  • 1Department of Plant Pathology and Microbiology, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.

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Natural product biosynthesis (NPB) enzymes evolve through innovation, with new activities and scaffolds emerging. These enzymes, initially specific, become multifunctional, producing diverse products due to their evolutionary state.

Keywords:
Chemical diversityEnzyme evolutionGeneralistNatural products biosynthesisPromiscuity

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Area of Science:

  • Biochemistry
  • Evolutionary Biology
  • Enzymology

Background:

  • Natural product biosynthesis (NPB) drives evolutionary innovation in organisms.
  • Enzyme evolution is central to understanding NPB.
  • Organismal competition and environmental changes fuel this innovation.

Purpose of the Study:

  • To review enzyme evolution in natural product biosynthesis.
  • To explore the de novo emergence of enzymatic activity and scaffolds.
  • To examine models explaining NPB enzyme promiscuity and product diversity.

Main Methods:

  • Literature review of enzyme evolution in NPB.
  • Analysis of de novo emergence cases.
  • Discussion of current enzyme evolution models.

Main Results:

  • New enzymatic activities can arise in existing proteins.
  • Novel enzyme scaffolds can emerge through evolution.
  • NPB enzymes exhibit inherent promiscuity and produce multiple products.

Conclusions:

  • NPB enzymes may have evolved for specific products but exist in a multifunctional state.
  • This evolutionary state leads to the production of diverse natural products.
  • Understanding enzyme evolution is key to NPB research.