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  • Title: Insights into polyketide biosynthesis gained from repurposing antibiotic-producing polyketide synthases to produce fuels and chemicals.
    Author: Yuzawa S, Keasling JD, Katz L.
    Journal: J Antibiot (Tokyo); 2016 Jul; 69(7):494-9. PubMed ID: 27245558.
    Abstract:
    Complex polyketides comprise a large number of natural products that have broad application in medicine and agriculture. They are produced in bacteria and fungi from enzyme complexes named type I polyketide synthases (PKSs) that are composed of multifunctional polypeptides containing discrete enzymatic domains organized into modules. The modular nature of PKSs has enabled a multitude of efforts to engineer the PKS genes to produce novel polyketides with enhanced or new properties. We have repurposed PKSs, employing up to three modules to produce a number of short-chain molecules that could have applications as fuels or industrial chemicals. Examining the enzymatic functions in vitro of these repurposed PKSs, we have uncovered a number of expanded substrate specificities and requirements of various PKS domains not previously reported and determined an unexpected difference in the order of enzymatic reactions within a module. In addition, we were able to efficiently change the stereochemistry of side chains in selected PKS products.
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