Insights into polyketide biosynthesis gained from repurposing antibiotic-producing polyketide synthases to produce fuels and chemicals

J Antibiot (Tokyo). 2016 Jul;69(7):494-9. doi: 10.1038/ja.2016.64. Epub 2016 Jun 1.

Abstract

Complex polyketides comprise a large number of natural products that have broad application in medicine and agriculture. They are produced in bacteria and fungi from enzyme complexes named type I polyketide synthases (PKSs) that are composed of multifunctional polypeptides containing discrete enzymatic domains organized into modules. The modular nature of PKSs has enabled a multitude of efforts to engineer the PKS genes to produce novel polyketides with enhanced or new properties. We have repurposed PKSs, employing up to three modules to produce a number of short-chain molecules that could have applications as fuels or industrial chemicals. Examining the enzymatic functions in vitro of these repurposed PKSs, we have uncovered a number of expanded substrate specificities and requirements of various PKS domains not previously reported and determined an unexpected difference in the order of enzymatic reactions within a module. In addition, we were able to efficiently change the stereochemistry of side chains in selected PKS products.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / biosynthesis
  • Biofuels
  • Catalytic Domain
  • Polyketide Synthases / chemistry*
  • Polyketide Synthases / genetics
  • Polyketide Synthases / metabolism
  • Polyketides / metabolism*
  • Protein Engineering
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Anti-Bacterial Agents
  • Biofuels
  • Polyketides
  • Polyketide Synthases