Enzyme-Loaded Nanoreactors Enable the Continuous Regeneration of Nicotinamide Adenine Dinucleotide in Artificial Metabolisms

Seong-Min Jo, Frederik R. Wurm*, Katharina Landfester*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)
55 Downloads (Pure)


Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme for numerous biocatalytic pathways. While in nature, NAD+ is continuously regenerated from NADH by enzymes, all synthetic NAD+ regeneration strategies require a continuous supply of expensive reagents and generate byproducts, making these strategies unattractive. In contrast, we present an artificial enzyme combination that produces NAD+ from oxygen and water continuously; no additional organic substrates are required once a minimal amount pyruvate is supplied. Three enzymes, i.e., LDH, LOX, and CAT, are covalently encapsulated into a substrate-permeable silica nanoreactor by a mild fluoride-catalyzed sol–gel process. The enzymes retain their activity inside of the nanoreactors and are protected against proteolysis and heat. We successfully used NAD+ from the nanoreactors for the continuous production of NAD+ i) to sense glucose in artificial glucose metabolism, and ii) to reduce the non-oxygen binding methemoglobin to oxygen-binding hemoglobin. This latter conversion might be used for the treatment of Methemoglobinemia. We believe that this versatile tool will allow the design of artificial NAD+-dependent metabolisms or NAD+-mediated redox-reactions.
Original languageEnglish
Pages (from-to)7728-7734
Number of pages7
JournalAngewandte Chemie (international edition)
Issue number14
Publication statusPublished - 29 Mar 2021


  • UT-Hybrid-D
  • encapsulation
  • enzyme reactions
  • nanoreactors
  • nicotinamide adenine dinucleotide
  • artificial metabolism


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