Natural Compounds as Pharmaceuticals: The Key Role of Cytochromes P450 Reactivity

Trends Biochem Sci. 2020 Jun;45(6):511-525. doi: 10.1016/j.tibs.2020.03.004. Epub 2020 Apr 5.

Abstract

The design of drugs from natural products is a re-emerging area due to the need for bioactive compounds. The exploitation of natural products and their derivatives obtained by biocatalysis is in line with the higher attention given today to new sustainable technologies that better preserve the environment (green chemistry). The research field of cytochromes P450 (CYPs) is continuously providing new enzymes and mutants that produce metabolites suitable for late-stage functionalization for new potential drugs. This review provides an overview of the exploitation of CYPs as biocatalysts in drug synthesis. Additionally, recent progress in protein and metabolic engineering is provided to show how these enzymes offer a toolbox that can be combined with other biocatalytic or chemical processes to build new platforms for the green production of new drugs.

Keywords: CYPs; biocatalysis; drug leads; late-stage functionalization; natural products.

Publication types

  • Review

MeSH terms

  • Biocatalysis
  • Biological Products / pharmacology*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Oxidation-Reduction
  • Pharmaceutical Preparations*
  • Protein Engineering
  • Substrate Specificity

Substances

  • Biological Products
  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System