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Engineering an Extremely Hybrid PKS for Adipic Acid Production.

Sarah H Klass1,2,3, Zilong Wang1,2,3, Nathan Lanclos1,2,4

  • 1Joint BioEnergy Institute, Emeryville, California 94608, United States.

ACS Synthetic Biology
|June 24, 2026
PubMed
Summary

Researchers engineered a novel polyketide synthase (PKS) pathway for adipic acid (AA) production. This breakthrough enables the biocatalytic synthesis of AA, a key nylon monomer, using a highly engineered PKS system.

Keywords:
Pseudomonas putidabiomanufacturingdicarboxylic acidsmetabolic engineeringmodular enzyme engineeringpolyketide synthases (PKSs)

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Area of Science:

  • Biochemistry
  • Synthetic Biology
  • Metabolic Engineering

Background:

  • Polyketide synthases (PKSs) are versatile modular enzymes.
  • PKSs are valuable biocatalysts for producing non-native compounds.
  • Adipic acid (AA) is an important industrial monomer for nylon production.

Purpose of the Study:

  • To engineer the first PKS-based pathway for adipic acid (AA) production.
  • To develop a novel biocatalytic route for AA synthesis.
  • To expand the PKS toolkit for producing dicarboxylic acids.

Main Methods:

  • Retrosynthetic analysis to identify key PKS modules.
  • Engineering a succinyl-CoA-loading module (EtnB) that retains the terminal carboxyl group.
  • Constructing a highly chimeric PKS by integrating domains from multiple organisms.
  • Functional expression in *Escherichia coli* and *Pseudomonas putida*.
  • Optimizing extender unit supply and host metabolism.

Main Results:

  • Successful engineering of a PKS pathway for adipic acid production.
  • Demonstrated selective succinyl-CoA loading *in vivo* using the EtnB module.
  • Achieved functional expression of a highly chimeric PKS with domains from seven modules across six non-natural junctions.
  • Enhanced AA titers through additional engineering strategies.

Conclusions:

  • Highly chimeric PKS systems can be functionally engineered through rational design.
  • The carboxyl-retaining EtnB module expands the PKS toolkit for dicarboxylic acid synthesis.
  • This work establishes a versatile platform for engineering diacids and other noncanonical products using PKS pathways.