title: Progress challenges and opportunities for the re-engineering of trans-AT polyketide synthases.
abstract: 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.
authors.affiliation: School of Biochemistry, Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK.
authors.forename: M
authors.initials: M
authors.lastname: Till
authors.forename: P R
authors.initials: PR
authors.lastname: Race
mesh_terms: D001709:Biotechnology; D048630:Polyketide Synthases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D015202:Protein Engineering
chemical_list: D048630:Polyketide Synthases