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Biosynthesis of α-substituted β-ketoesters via the tandem Knoevenagel condensation-reduction reaction using a single enzyme
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  • Xiaolong Liu,
  • Xiangjie Li,
  • Zhelun Wang,
  • Jinlong Zhou,
  • Xinjiong Fan,
  • Yao Fu
Xiaolong Liu
University of Science and Technology of China
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Xiangjie Li
University of Science and Technology of China
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Zhelun Wang
University of Science and Technology of China
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Jinlong Zhou
University of Science and Technology of China
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Xinjiong Fan
Anhui Medical University
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Yao Fu
University of Science and Technology of China
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Abstract

Saturated α-substituted β ketoesters are important building blocks in synthesis of pharmaceuticals and agrochemicals. Herein, we report a one-pot biosynthesis of α-substituted β ketoesters via Knoevenagel condensation and reduction of received unsaturated alkenes in situ, catalyzed by single ene-reductase (NerA). A series of inexpensive and readily available aldehydes and 1,3-diketones were condensed and reduced by NerA in aqueous solution at room temperature. We also note that low loadings (3 mg/ml) of NerA are sufficient to facilitate the cascade process, both E and Z isomeric intermediates can be reduced effectively and improved the overall yield up to 95%. Meanwhile, the method can be applied in preparative-scale synthesis of pharmaceutical intermediate. This process conforms to the concepts of green chemistry and shows advantages for synthesis of high value saturated α-substituted β ketoesters.