Progress challenges and opportunities for the re-engineering of trans-AT polyketide synthases

M Till, P R Race

Research output: Contribution to journalReview article (Academic Journal)peer-review


Polyketides are a structurally and functionally diverse family of bioactive natural products that are used extensively as pharmaceuticals and agrochemicals. In bacteria these molecules are biosynthesized by giant, multi-functional enzymatic complexes, termed modular polyketide synthases (PKSs), that function in assembly-line like fashion to fuse and tailor simple carboxylic acid monomers into a vast array of elaborate chemical scaffolds. Modifying PKSs through targeted synthase re-engineering is a promising approach for accessing functionally-optimized polyketides. Due to their highly mosaic architectures the recently identified trans-AT family of modular synthases appear inherently more amenable to re-engineering than their well studied cis-AT counterparts. Here, we review recent progress in the re-engineering of trans-AT PKSs, summarize opportunities for harnessing the biosynthetic potential of these systems, and highlight challenges that such re-engineering approaches present.

Original languageEnglish
Pages (from-to)877-88
Number of pages12
JournalBiotechnology Letters
Issue number5
Publication statusPublished - May 2014

Structured keywords

  • Bristol BioDesign Institute


  • Biotechnology
  • Polyketide Synthases/chemistry
  • Protein Engineering

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