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

Lookup NU author(s): Professor Paul RaceORCiD

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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. © 2014 Springer Science+Business Media Dordrecht.

Publication metadata

Author(s): Till M, Race PR

Publication type: Review

Publication status: Published

Journal: Biotechnology Letters

Year: 2014

Volume: 36

Issue: 5

Pages: 877-888

Print publication date: 01/05/2014

Online publication date: 21/02/2014

Acceptance date: 23/12/2013

ISSN (print): 0141-5492

ISSN (electronic): 1573-6776

Publisher: Kluwer Academic Publishers

URL: https://doi.org/10.1007/s10529-013-1449-2

DOI: 10.1007/s10529-013-1449-2

PubMed id: 24557077

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