What does this research mean for the field?

A targeted strategy utilizing phosphite and polymyxin B enables the near-complete, selective intracellular reduction of the non-natural cofactor nicotinamide cytosine dinucleotide (NCD) without disrupting natural NAD/NADP pools, establishing NCD as a viable independent redox cofactor for artificial biosynthesis. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To develop a selective intracellular reduction strategy for the synthetic cofactor nicotinamide cytosine dinucleotide to power targeted biosynthetic reactions without disrupting native metabolic networks.

August 31, 2026BiomoleculesOpen Access

Selective Redox Tuning Enables Potent Intracellular Reduction of Nicotinamide Cytosine Dinucleotide

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Authors

XGXiaojia GuoDalian University of Technology YHYanzhe HuangDalian Institute of Chemical Physics YHYinghan HuDalian Institute of Chemical Physics

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Implication

Experimental study demonstrates selective reduction of the synthetic cofactor nicotinamide cytosine dinucleotide in Escherichia coli, indicating a viable orthogonal system for biosynthesis.

Key Points

To develop a selective intracellular reduction strategy for the synthetic cofactor nicotinamide cytosine dinucleotide to power targeted biosynthetic reactions without disrupting native metabolic networks.
Validated specific coupled enzymatic colorimetric assays to independently quantify intracellular NAD, NADP, and NCD pools.
Utilized phosphite as an energy source in cell-free systems and living Escherichia coli to drive cofactor reduction.
Treated bacterial cells with polymyxin B to overcome membrane transport barriers and facilitate phosphite uptake.
Phosphite-driven reduction selectively elevated intracellular NCDH without perturbing endogenous NADH/NAD and NADPH/NADP ratios.
Cell-free systems confirmed that phosphite could drive near-complete reduction of NCD.
Polymyxin B treatment enabled enhanced phosphite uptake in E. coli, achieving an intracellular NCDH/NCD ratio of 47, which represents 98% of the intracellular NCD pool in the reduced form.

Cite This Study

Guo et al. (2026) studied this question.

synapsesocial.com/papers/6a95427bf20e493292a74dbd https://doi.org/10.3390/biom16091255

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Implication

Experimental study demonstrates selective reduction of the synthetic cofactor nicotinamide cytosine dinucleotide in Escherichia coli, indicating a viable orthogonal system for biosynthesis.

Selective Redox Tuning Enables Potent Intracellular Reduction of Nicotinamide Cytosine Dinucleotide

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Implication

Key Points

Cite This Study

Selective Redox Tuning Enables Potent Intracellular Reduction of Nicotinamide Cytosine Dinucleotide

Discussion

Member takes

Implication

Key Points

Cite This Study

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