Technical Advances to Accelerate Modular Type I Polyketide Synthase Engineering towards a Retro-biosynthetic Platform

Bo Pang, Luis E. Valencia, Jessica Wang, Yao Wan, Ravi Lal, Amin Zargar, Jay D. Keasling

Research output: Contribution to journalJournal articleResearchpeer-review


Modular type I polyketide synthases (PKSs) are multifunctional proteins that are comprised of individual domains organized into modules. These modules act together to assemble complex polyketides from acyl-CoA substrates in a linear fashion. This assembly-line enzymology makes engineered PKSs a potential retro-biosynthetic platform to produce fuels, commodity chemicals, speciality chemicals, and pharmaceuticals in various host microorganisms, including bacteria and fungi. However, the realization of this potential is restricted by practical difficulties in strain engineering, protein overexpression, and titer/yield optimization. These challenges are becoming more possible to overcome due to technical advances in PKS design, engineered heterologous hosts, DNA synthesis and assembly, PKS heterologous expression, and analytical methodology. In this review, we highlight these technical advances in PKS engineering and provide practical considerations thereof.
Original languageEnglish
JournalBiotechnology and Bioprocess Engineering
Issue number3
Pages (from-to)413-423
Publication statusPublished - 2019


  • Polyketide synthase
  • Retro-biosynthetic analysis
  • Protein engineering
  • Heterologous expression
  • Biofuels
  • Bioproducts

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