Light-Driven NADPH Cofactor Recycling by Photosystem I for Biocatalytic Reactions

Hitesh Medipally, Alice Guarneri, Lars Pospisil, Maurice C.R. Franssen, Willem J.H. van Berkel, Caroline E. Paul, Marc M. Nowaczyk*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

Biocatalytic asymmetric reduction of C=C and C=O bonds is highly attractive to produce valuable (chiral) chemicals for the fine and pharmaceutical industry, yet occurs at the expense of reduced nicotinamide adenine dinucleotide coenzyme NADPH that requires recycling. Established methods each have their challenges. Here we developed a light-driven approach based on photosystem I (PSI) by mimicking the natural electron transfer from PSI via ferredoxin (Fd) towards ferredoxin NADP+ reductase (FNR) in vitro. Illumination with red light led to reduction of NADP+ to NADPH with a turnover frequency of 2.55 s−1 (>9000 h−1) at pH 7.5. Light-driven NADPH regeneration by PSI-Fd-FNR was coupled with three oxidoreductases for asymmetric reduction of C=C and C=O bonds, reaching up to 99 % conversion with a turnover number of 3035, and retaining enantioselectivity. This study demonstrates the capacity of a PSI system to drive continuous NADPH-dependent biocatalytic conversions with light.

Original languageEnglish
Article numbere202300821
JournalChemCatChem
Volume15
Issue number18
DOIs
Publication statusPublished - 2023

Keywords

  • biocascades
  • enzymatic reduction
  • ferredoxin NADP oxidoreductase
  • NADPH cofactor regeneration
  • photobiocatalysis

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