BioChem - DOS

Employing Modular Polyketide Synthase Ketoreductases as Biocatalysts in the Preparative Chemoenzymatic Syntheses of Diketide Chiral Building Blocks

Chemistry & biology

Piasecki, Shawn K.; Taylor, Clint A.; Detelich, Joshua F.; Liu, J.; Zheng, J.; Komsoukaniants, A.; Siegel, Dionicio R.; Keatinge-Clay, Adrian T.

Chiral building blocks are valuable intermediates in the syntheses of natural products and pharmaceuticals. A scalable chemoenzymatic route to chiral diketides has been developed that includes the general synthesis of α-substituted, β-ketoacyl N-acetylcysteamine thioesters followed by a biocatalytic cycle in which a glucose-fueled NADPH-regeneration system drives reductions catalyzed by isolated modular polyketide synthase (PKS) ketoreductases (KRs). To identify KRs that operate as active, stereospecific biocatalysts, 11 isolated KRs were incubated with 5 diketides and their products were analyzed by chiral chromatography. KRs that naturally reduce small polyketide intermediates were the most active and stereospecific toward the panel of diketides. Several biocatalytic reactions were scaled up to yield more than 100 mg of product. These syntheses demonstrate the ability of PKS enzymes to economically and greenly generate diverse chiral building blocks on a preparative scale.

2011

Current Biology Ltd ; Elsevier Science Ltd

1074-5521

1879-1301

18

10

pp.1331-1340

10.1016/j.chembiol.2011.07.021

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