# Ferredoxin—NADP(+) reductase
**Ferredoxin—NADP(+) reductase** (FNR; EC 1.18.1.2) is a flavoenzyme that catalyzes the transfer of reducing equivalents between ferredoxin, an obligatory one-electron carrier, and NADP(H), an obligatory two-electron carrier[1](https://resource.odmu.edu.ua/chair/download/9074/FPHSQEeBRn9rgO4Y8KvfZA/Lennarz%20W.J.%2C%20Lane%20M.D.%20%28eds.%29%20-%20Encyclopedia%20of%20Biological%20Chemistry.%20Vol.%202%20%28AP%2C%202004%29.pdf). In oxygenic photosynthesis it performs the final step of the electron transport chain, reducing NADP+ to NADPH, the reducing power used for CO2 assimilation[2](https://febs.onlinelibrary.wiley.com/doi/10.1046/j.1432-1033.2003.03566.x). The name FNR is also applied to a broad group of related flavoenzymes found in bacteria, mitochondria, and apicoplasts of parasitic protists[1](https://resource.odmu.edu.ua/chair/download/9074/FPHSQEeBRn9rgO4Y8KvfZA/Lennarz%20W.J.%2C%20Lane%20M.D.%20%28eds.%29%20-%20Encyclopedia%20of%20Biological%20Chemistry.%20Vol.%202%20%28AP%2C%202004%29.pdf).
| Key fact | Detail |
|---|---|
| Classification | EC 1.18.1.2, a flavoenzyme family catalyzing reducing-equivalent transfer between NAD(P)H and ferredoxins[1](https://resource.odmu.edu.ua/chair/download/9074/FPHSQEeBRn9rgO4Y8KvfZA/Lennarz%20W.J.%2C%20Lane%20M.D.%20%28eds.%29%20-%20Encyclopedia%20of%20Biological%20Chemistry.%20Vol.%202%20%28AP%2C%202004%29.pdf) |
| Overall reaction | 2Fd (Fe2+) + NADP+ + H+ ⇌ 2Fd (Fe3+) + NADPH[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9687028/) |
| Structure | Monomeric protein with an FAD-binding domain and a Rossmann-fold NADP-binding domain[1](https://resource.odmu.edu.ua/chair/download/9074/FPHSQEeBRn9rgO4Y8KvfZA/Lennarz%20W.J.%2C%20Lane%20M.D.%20%28eds.%29%20-%20Encyclopedia%20of%20Biological%20Chemistry.%20Vol.%202%20%28AP%2C%202004%29.pdf) |
| Discovery | Isolated from pea chloroplasts in 1956 by Avron and Jagendorf as a NADPH-dependent diaphorase[1](https://resource.odmu.edu.ua/chair/download/9074/FPHSQEeBRn9rgO4Y8KvfZA/Lennarz%20W.J.%2C%20Lane%20M.D.%20%28eds.%29%20-%20Encyclopedia%20of%20Biological%20Chemistry.%20Vol.%202%20%28AP%2C%202004%29.pdf) |
| Physiological direction | Toward NADP+ reduction in photosynthetic FNRs; toward ferredoxin reduction in heterotrophic FNRs[1](https://resource.odmu.edu.ua/chair/download/9074/FPHSQEeBRn9rgO4Y8KvfZA/Lennarz%20W.J.%2C%20Lane%20M.D.%20%28eds.%29%20-%20Encyclopedia%20of%20Biological%20Chemistry.%20Vol.%202%20%28AP%2C%202004%29.pdf) |
| Protein families | Two unrelated families: plant-type FNRs and glutathione reductase-type FNRs[4](https://pubmed.ncbi.nlm.nih.gov/18307973/) |
| Iron-stress substitute | Flavodoxin, an FMN-containing protein, replaces ferredoxin in most cyanobacteria and some algae under low-iron conditions[5](https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2009.07122.x) |
## Role in photosynthesis
Electrons released by water splitting pass through photosystem II, plastoquinone, the cytochrome b6f complex, plastocyanin, and photosystem I to ferredoxin isoforms, which distribute them to several pathways[6](https://onlinelibrary.wiley.com/doi/full/10.1111%2Fpce.12046). Shortly after the chloroplast reductase was isolated, Shin and Arnon showed that its physiological role is to catalyze electron transfer from ferredoxin, reduced by photosystem I, to NADP+, and that this reaction provides the NADPH necessary for CO2 assimilation in plants and cyanobacteria[2](https://febs.onlinelibrary.wiley.com/doi/10.1046/j.1432-1033.2003.03566.x). The NADPH formed supplies reducing power for the regenerative step of the [Calvin cycle](https://www.edgepedia.org/calvin-cycle), the conversion of 1,3-bisphosphoglycerate into glyceraldehyde 3-phosphate, and for other biosynthetic, regulatory, and protective pathways[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC4400536/).
The photoreduction of NADP+ through FNR is the major system in the chloroplast for this purpose[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC8826907/). A 2024 study in the cyanobacterium *Synechocystis* sp. PCC 6803 found that FNR is the preferred route for delivering photosynthetic electrons from reduced ferredoxin, outcompeting alternative electron valves such as the flavodiiron protein-driven Mehler-like reaction and cyclic electron transport; the cellular NADPH/NADP+ ratio acts as a key factor orchestrating photosynthetic electron flux[9](https://pubmed.ncbi.nlm.nih.gov/39008444/).
## Structure and families
FNR is a monomeric protein of two domains, one binding the FAD cofactor and a Rossmann fold binding NADP+/NADPH[1](https://resource.odmu.edu.ua/chair/download/9074/FPHSQEeBRn9rgO4Y8KvfZA/Lennarz%20W.J.%2C%20Lane%20M.D.%20%28eds.%29%20-%20Encyclopedia%20of%20Biological%20Chemistry.%20Vol.%202%20%28AP%2C%202004%29.pdf). Although all FNRs catalyze the same reaction, they belong to two unrelated protein families: the plant-type FNRs and the glutathione reductase-type FNRs[4](https://pubmed.ncbi.nlm.nih.gov/18307973/). The glutathione reductase-type enzymes, found in mitochondria and some bacterial genera, belong to the structural superfamily of disulfide oxidoreductases whose prototype is glutathione reductase; the plant-type family, comprising FNRs from plastids and most eubacteria, is unrelated in sequence to the former[10](https://www.sciencedirect.com/science/article/abs/pii/S1570963903003923).
**Two functional classes.** Plant-type FNRs divide into a plastidic class, characterized by an extended FAD conformation and high catalytic efficiency, and a bacterial class with a folded FAD molecule and low turnover rates; sequence alignments support this classification and provide a criterion for predicting the properties of newly identified members[10](https://www.sciencedirect.com/science/article/abs/pii/S1570963903003923). In cyanobacteria, two isoforms are known: a small FNR(S) similar to the plant plastid enzyme and a large FNR(L) with an additional N-terminal domain; FNR(L) mainly performs photoreduction of NADP+, whereas FNR(S) has other roles[11](https://www.osti.gov/servlets/purl/2583961). In higher plants, distinct leaf-type and root-type isoforms operate in photosynthetic and non-photosynthetic tissues respectively[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9687028/).
## Catalytic mechanism
FNR catalyzes the reversible transfer of reducing equivalents between the obligatory one-electron carrier ferredoxin and the obligatory two-electron carrier NADP(H), with the enzyme-bound FAD cycling among oxidized, semiquinone, and fully reduced states during turnover[12](https://lib.ysu.am/disciplines_bk/805d395f44c0cf59106381105a8f11ea.pdf). The overall photosynthetic reaction is[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9687028/):
\[ 2\,\mathrm{Fd}_{\mathrm{red}} + \mathrm{NADP}^{+} + \mathrm{H}^{+} \rightleftharpoons 2\,\mathrm{Fd}_{\mathrm{ox}} + \mathrm{NADPH} \]
In the leaf enzyme, electrons flow in the sequence photosystem I → Fd I [2Fe-2S] (−401 mV) → LFNR (FAD) → NADP+ (−320 mV)[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9687028/). The catalytic cycle for this system was proposed by Batie and Kamin in 1984 and involves one-electron transfer, proton-coupled one-electron transfer, and two-electron hydride transfer steps: reduced ferredoxin delivers one electron to FAD, a second reduced ferredoxin delivers another, and NADP+ then accepts a hydride from FADH− to form NADPH[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9687028/). Rapid-mixing experiments showed that in a mixture of the three components, oxidation of reduced FNR by NADP+ is faster than electron transfer from reduced ferredoxin to the reductase, which is the main empirical support for this reaction order[2](https://febs.onlinelibrary.wiley.com/doi/10.1046/j.1432-1033.2003.03566.x).
**Active-site residues.** In the spinach enzyme, the isoalloxazine ring of FAD is sandwiched between two aromatic residues, Tyr314 and Tyr95, and the C-terminal Tyr314 must move away for productive hydride transfer from reduced FAD to NADP+; a conserved Ser96-Glu312 pair modulates affinity for NADP+, stabilization of the FAD semiquinone, and the rate of electron transfer[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9687028/). A conserved glutamate in the active site has a rationalized role in the reaction mechanism of plant-type FNRs[13](https://bisb.uni-bayreuth.de/PDF/Dumit2010.JMB397-814.pdf).
## Ferredoxin, flavodoxin, and electron partitioning
FNR works with ferredoxin, a small iron-sulfur protein, as its one-electron partner. Under iron-limiting conditions in most cyanobacteria and some algae, flavodoxin, an FMN-containing flavoprotein, substitutes for the ferredoxin pair in the reaction[5](https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2009.07122.x). The FNR-Fd and FNR-Fld complex pairs switch between one-electron and two-electron transfer through FAD semiquinone intermediates[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9687028/).
Because reduced ferredoxin distributes electrons to many pathways, including cyclic photophosphorylation, nitrogen assimilation, and the thioredoxin system, FNR competes with other acceptors at the acceptor side of photosystem I[14](https://www.mdpi.com/2075-1729/4/4/666). Distinct ferredoxin isoforms can channel electrons preferentially: in maize, minor ferredoxin types show properties favoring donation to an acceptor involved in cyclic electron flow over support of NADP+ photoreduction[15](https://pmc.ncbi.nlm.nih.gov/articles/PMC4030315/).
## History and wider family
Avron and Jagendorf identified FNR for the first time in 1956, isolating from pea chloroplasts an enzyme that functions as a diaphorase requiring NADPH: a flavin-bearing protein that moves reducing equivalents from NADPH onto a range of electron acceptors.[1](https://resource.odmu.edu.ua/chair/download/9074/FPHSQEeBRn9rgO4Y8KvfZA/Lennarz%20W.J.%2C%20Lane%20M.D.%20%28eds.%29%20-%20Encyclopedia%20of%20Biological%20Chemistry.%20Vol.%202%20%28AP%2C%202004%29.pdf) Working on the same problem, [Anthony San Pietro](https://www.edgepedia.org/anthony-san-pietro) and Horace Lang characterized an enzyme generating NADPH via reduced ferredoxin and, based on its properties and role in photosynthesis, suggested the name "photosynthetic pyridine nucleotide reductase"[16](https://www.esalq.usp.br/lepse/imgs/conteudo_thumb/J--Biol--Chem--2005-Kresge-e48.pdf).
After the chloroplast enzyme was isolated, flavoproteins with FNR activity were found in phototrophic and heterotrophic bacteria, animal and yeast mitochondria, and the apicoplasts of obligate intracellular parasites[2](https://febs.onlinelibrary.wiley.com/doi/10.1046/j.1432-1033.2003.03566.x). FNR is regarded as the prototype for a large family of flavin-containing enzymes with similar structures and reaction mechanisms[2](https://febs.onlinelibrary.wiley.com/doi/10.1046/j.1432-1033.2003.03566.x); FNR-like and flavodoxin-like domains also occur in eukaryotic NAD(P)H-dependent enzymes such as cytochrome P450 reductase and nitric oxide synthase isoforms[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC9687028/). Characterization of an FNR from the malaria parasite *Plasmodium falciparum* brought these enzymes into the field of drug design[4](https://pubmed.ncbi.nlm.nih.gov/18307973/).
## References
1. [Ferredoxin-NADP+ Reductase, Encyclopedia of Biological Chemistry (Lennarz & Lane, eds., 2004)](https://resource.odmu.edu.ua/chair/download/9074/FPHSQEeBRn9rgO4Y8KvfZA/Lennarz%20W.J.%2C%20Lane%20M.D.%20%28eds.%29%20-%20Encyclopedia%20of%20Biological%20Chemistry.%20Vol.%202%20%28AP%2C%202004%29.pdf)
2. [Carrillo et al. (2003). Open questions in ferredoxin-NADP+ reductase catalytic mechanism. European Journal of Biochemistry.](https://febs.onlinelibrary.wiley.com/doi/10.1046/j.1432-1033.2003.03566.x)
3. [Iyanagi (2022). Roles of Ferredoxin-NADP+ Oxidoreductase and Flavodoxin in NAD(P)H-Dependent Electron Transfer Systems. Antioxidants 11(11):2143.](https://pmc.ncbi.nlm.nih.gov/articles/PMC9687028/)
4. [Aliverti et al. (2008). Structural and functional diversity of ferredoxin-NADP+ reductases. Archives of Biochemistry and Biophysics 474(2):283-291.](https://pubmed.ncbi.nlm.nih.gov/18307973/)
5. [Medina (2009). Structural and mechanistic aspects of flavoproteins: photosynthetic electron transfer from photosystem I to NADP+. The FEBS Journal.](https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2009.07122.x)
6. [Hanke & Mulo (2013). Plant type ferredoxins and ferredoxin-dependent metabolism. Plant, Cell & Environment.](https://onlinelibrary.wiley.com/doi/full/10.1111%2Fpce.12046)
7. [The long goodbye: the rise and fall of flavodoxin during plant evolution (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC4400536/)
8. [Forty years of the structure of plant-type ferredoxin (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC8826907/)
9. [Strong heterologous electron sink outcompetes alternative electron transport pathways in photosynthesis (PubMed, 2024)](https://pubmed.ncbi.nlm.nih.gov/39008444/)
10. [Ceccarelli et al. (2003). Functional plasticity and catalytic efficiency in plant and bacterial ferredoxin-NADP(H) reductases. Biochimica et Biophysica Acta.](https://www.sciencedirect.com/science/article/abs/pii/S1570963903003923)
11. [EPR studies of ferredoxin in spinach and cyanobacteria (OSTI)](https://www.osti.gov/servlets/purl/2583961)
12. [Ferredoxin-NADP+ Reductase, Encyclopedia of Biological Chemistry (catalytic mechanism chapter)](https://lib.ysu.am/disciplines_bk/805d395f44c0cf59106381105a8f11ea.pdf)
13. [Dumit et al. (2010). Mechanistic Insights into Ferredoxin–NADP(H) Reductase Catalysis Involving the Conserved Glutamate in the Active Site. Journal of Molecular Biology 397:814.](https://bisb.uni-bayreuth.de/PDF/Dumit2010.JMB397-814.pdf)
14. [Function and Regulation of Ferredoxins in the Cyanobacterium, Synechocystis PCC6803: Recent Advances. Life 4(4):666.](https://www.mdpi.com/2075-1729/4/4/666)
15. [The End of the Line: Can Ferredoxin and Ferredoxin NADP(H) Oxidoreductase Determine the Fate of Photosynthetic Electrons? (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC4030315/)
16. [Kresge et al. (2005). The Discovery of Ferredoxin and Its Role in Photosynthesis: the Work of Anthony San Pietro. Journal of Biological Chemistry.](https://www.esalq.usp.br/lepse/imgs/conteudo_thumb/J--Biol--Chem--2005-Kresge-e48.pdf)
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*Topic: Encyclopedia › Life and health › Biological foundations › Biochemistry and metabolism › Enzyme classes and activities › Oxidoreductases, dehydrogenases, and cytochrome P450 › Electron-transfer partner proteins of oxidoreductases*
*Initially written Sep 17, 2026 · Reviewed: Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license