Programming Super DNA-Enzyme Molecules for On-Demand Enzyme Activity Modulation

Angew Chem Int Ed Engl. 2023 Mar 27;62(14):e202214450. doi: 10.1002/anie.202214450. Epub 2023 Feb 23.

Abstract

Dynamic interactions of enzymes, including programmable configuration and cycling of enzymes, play important roles in the regulation of cellular metabolism. Here, we constructed a super DNA-enzymes molecule (SDEM) that comprises at least two cascade enzymes and multiple linked DNA strands to control and detect metabolism. We found that the programmable SDEM, which comprises glucose oxidase (GOx) and horseradish peroxidase (HRP), has a 20-fold lower detection limit and a 1.6-fold higher reaction rate than free enzymes. An SDEM can be assembled and disassembled using a hairpin structure and a displacement DNA strand to complete multiple cycles. An entropically driven catalytic assembly (catassembly) enables different SDEMs to switch from an SDEM with GOx and HRP cascades to an SDEM with sarcosine oxidase (SOX) and HRP cascades in over six orders of magnitude less time than without the catassembly to detect different metabolisms (GO and sarcosine) on demand.

Keywords: Catassembly; Enzyme Cascade; Programmable Modulation; SDEM; Strand Displacement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • DNA* / chemistry
  • Enzymes, Immobilized* / chemistry
  • Glucose Oxidase / metabolism
  • Horseradish Peroxidase / chemistry

Substances

  • Enzymes, Immobilized
  • DNA
  • Glucose Oxidase
  • Horseradish Peroxidase