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Flavin mononucleotide
Flavin mononucleotide
Flavin mononucleotide
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Flavin mononucleotide
Skeletal formula of flavin mononucleotide
Ball-and-stick model of the flavin mononucleotide molecule
Names
IUPAC name
1-Deoxy-1-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)-D-ribitol 5-(dihydrogen phosphate)
Systematic IUPAC name
(2R,3S,4S)-5-(7,8-Dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)-2,3,4-trihydroxypentyl dihydrogen phosphate
Other names
  • FMN
  • Epioxa
  • Epioxa HD
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.150 Edit this at Wikidata
E number E101a (colours)
MeSH Flavin+mononucleotide
UNII
  • InChI=1S/C17H21N4O9P/c1-7-3-9-10(4-8(7)2)21(15-13(18-9)16(25)20-17(26)19-15)5-11(22)14(24)12(23)6-30-31(27,28)29/h3-4,11-12,14,22-24H,5-6H2,1-2H3,(H,20,25,26)(H2,27,28,29)/t11-,12+,14-/m0/s1
    Key: FVTCRASFADXXNN-SCRDCRAPSA-N
  • Cc1cc2c(cc1C)n(c-3nc(=O)[nH]c(=O)c3n2)C[C@@H]([C@@H]([C@@H](COP(=O)(O)O)O)O)O
Properties
C17H21N4O9P
Molar mass 456.344 g/mol
Melting point 195 °C
Pharmacology
S01XA26 (WHO)
Ophthalmic
Legal status
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as the prosthetic group of various oxidoreductases, including NADH dehydrogenase, as well as a cofactor in biological blue-light photo receptors.[2] During the catalytic cycle, various oxidoreductases induce reversible interconversions between the oxidized (FMN), semiquinone (FMNH•), and reduced (FMNH2) forms of the isoalloxazine core. FMN is a stronger oxidizing agent than NAD and is particularly useful because it can take part in both one- and two-electron transfers. In its role as blue-light photo receptor, (oxidized) FMN stands out from the 'conventional' photo receptors as the signaling state and not an E/Z isomerization.

It is the principal form in which riboflavin is found in cells and tissues. It requires more energy to produce, but is more soluble than riboflavin. In cells, FMN occurs freely circulating but also in several covalently bound forms.[3] Covalently or non-covalently bound FMN is a cofactor of many enzymes playing an important pathophysiological role in cellular metabolism. For example dissociation of flavin mononucleotide from mitochondrial complex I has been shown to occur during ischemia/reperfusion brain injury during stroke.[4][5]

Food additive

[edit]

Flavin mononucleotide is also used as an orange-red food colour additive, designated in Europe as E number E101a.[6]

E106, a very closely related food dye, is riboflavin-5′-phosphate sodium salt, which consists mainly of the monosodium salt of the 5′-monophosphate ester of riboflavin. It is rapidly turned to free riboflavin after ingestion. It is found in many foods for babies and young children as well as jams, milk products, and sweets and sugar products.[7]

Medical uses

[edit]
Flavin mononucleotide
Clinical data
AHFS/Drugs.comEpioxa
License data
Identifiers
DrugBank
E numberE101a (colours) Edit this at Wikidata
CompTox Dashboard (EPA)
ECHA InfoCard100.005.150 Edit this at Wikidata

Riboflavin 5'-phosphate (Epioxa) and riboflavin 5’-phosphate sodium (Epioxa HD) and are photoenhancers that are indicated for use in epithelium-on corneal collagen cross-linking for the treatment of keratoconus in people aged thirteen years of age and older, in conjunction with the O2n System and the Boost Goggles.[1]

Flavin mononucleotide, or riboflavin-5'-phosphate, is a biomolecule produced from riboflavin by the enzyme riboflavin kinase and functions as prosthetic group of various oxidoreductases including NADH dehydrogenase as well as cofactor in biological blue-light photo receptors.[8] Riboflavin 5'-phosphate sodium is a mixture of the sodium salts of riboflavin, riboflavin monophosphates, and riboflavin diphosphates.[1]

Epioxa and Epioxa HD were approved for medical use in the United States in October 2025.[9]

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Flavin mononucleotide

View on Grokipedia
from Grokipedia
Flavin mononucleotide (FMN), also known as riboflavin 5'-phosphate, is a phosphorylated derivative of (vitamin B₂) in which the primary hydroxyl group of the ribitol side chain is esterified with , forming a key with the C₁₇H₂₁N₄O₉P and a molecular weight of 456.3 g/mol. As a vital coenzyme and in flavoenzymes, FMN plays an essential role in facilitating one- and two-electron oxidation/reduction reactions critical to cellular , including energy production and the of fatty acids, , and carbohydrates. It serves as the principal intracellular form of , functioning as an intermediate in the of (FAD) and directly participating in processes, such as electron transfer from NADH to iron-sulfur clusters in mitochondrial complex I of the . FMN is synthesized from via the riboflavin kinase and is found in all living organisms, underscoring its universal importance in aerobic and anaerobic metabolic pathways.

Chemical identity

Nomenclature and formula

Flavin mononucleotide, commonly abbreviated as FMN, is the phosphorylated derivative of (vitamin B₂) at the 5' position of its ribitol side chain. Its systematic International Union of Pure and Applied Chemistry (IUPAC) name is {[(2R,3S,4S)-5-(7,8-dimethyl-2,4-dioxo-2H,3H,4H,10H-benzopteridin-10-yl)-2,3,4-trihydroxypentyl]oxy}phosphonic acid. Other widely used names include 5'-phosphate and vitamin B₂ phosphate. The molecular formula of FMN is C17H21N4O9PC_{17}H_{21}N_4O_9P, reflecting the isoalloxazine ring system of riboflavin esterified with a phosphate group on the terminal carbon of the ribitol chain. This structure yields a molar mass of 456.34 g/mol. The compound is identified by CAS Registry Number 146-17-8 in chemical databases. The nomenclature of FMN emerged in the 1930s amid pioneering research on flavoproteins, where biochemist Hugo Theorell isolated and characterized it in 1937 as the phosphate ester of , establishing "flavin mononucleotide" as the standard term for this coenzyme form. This naming convention distinguished FMN from free and the dinucleotide , facilitating its recognition in enzymatic studies.

Molecular structure

Flavin mononucleotide (FMN) features a core isoalloxazine ring system, which consists of a fused pteridine-like structure incorporating and rings, with methyl substitutions at positions 7 and 8 to enhance its stability and properties. This planar, conjugated heterocyclic system forms the redox-active center of the molecule, characterized by delocalized π-electrons and specific alternations that facilitate . Attached to the N-10 position of the isoalloxazine ring is a ribitol side chain, a linear five-carbon polyol derived from ribose, which terminates in a phosphate group esterified at the 5' carbon via a P-O-C bond. This phosphate ester linkage imparts polarity and solubility to FMN, distinguishing it from its precursor riboflavin. The overall molecular formula of FMN is C17H21N4O9PC_{17}H_{21}N_4O_9P. In comparison to (FAD), FMN lacks the connected via a bridge, resulting in a simpler mononucleotide structure that still retains the essential isoalloxazine core for biological function. The text-based structural representation emphasizes the isoalloxazine as the central scaffold: a ring with N atoms at key positions (1,3,5,10), flanked by the substituted ring and the ribitol-phosphate chain.

Physical and chemical properties

Solubility and stability

Flavin mononucleotide (FMN), particularly in its sodium salt form, exhibits high , reaching approximately 92 g/L at , primarily attributed to its group, which enhances polarity compared to , whose is only about 0.1 g/L under similar conditions. This property facilitates its use in aqueous biochemical assays and biological systems. The compound has a melting point of approximately 290 °C, at which it decomposes rather than forming a liquid phase. FMN demonstrates sensitivity to environmental factors affecting its stability: it undergoes photodegradation upon exposure to light, particularly UV, leading to breakdown of the isoalloxazine ring. It is most stable in the pH range of 4 to 7, where the phosphate and isoalloxazine moieties maintain integrity chemically, though photodegradation rates increase above pH 8; the phosphate ester undergoes hydrolysis primarily in acidic conditions (pH 3-7, maximum at pH 4) and in strongly alkaline conditions (pH >12). FMN shows sensitivity to heat, with decomposition accelerated during prolonged heating. The pKa values reflect these sensitivities: the phosphate group has pKa values of approximately 1.6 (first dissociation) and 6.2 (second), influencing and charge at physiological , while the isoalloxazine ring's N(3)-H has a pKa around 10, affecting in basic environments. For optimal handling and storage, FMN should be kept in dark, cool (ideally -20°C), and dry conditions to minimize , , and thermal breakdown.

Redox properties

Flavin mononucleotide (FMN) exhibits versatile chemistry due to its isoalloxazine ring system, which serves as the primary in reduction processes. This enables FMN to cycle through three distinct states: the oxidized form (FMN), the one-electron reduced semiquinone radical (FMNH•), and the fully reduced (FMNH₂). The oxidized state is characteristically , the semiquinone radical appears , and the reduced form is colorless. These states facilitate both one-electron and two-electron transfer mechanisms, allowing FMN to participate in a wide range of biological reactions. The standard reduction potential for the overall two-electron reduction of FMN to FMNH₂ at 7.0 and 20°C is -0.207 V (versus the ). This process follows the equation: FMN+2H++2e−⇌FMNH2\text{FMN} + 2\text{H}^+ + 2\text{e}^- \rightleftharpoons \text{FMNH}_2 The one-electron reductions occur sequentially: the first step from oxidized FMN to the semiquinone radical has a potential of -0.313 V, while the second step from the semiquinone to FMNH₂ is -0.101 V. These potentials reflect the relative stability of the semiquinone intermediate, which is less favored in free solution compared to protein-bound forms, influencing the preference for one- versus two-electron pathways. The potentials of FMN are sensitive to environmental factors, particularly , as states of the isoalloxazine ring affect ; for instance, potentials become more negative at higher due to . Protein binding further modulates these values, often shifting them positively by 100–200 mV to enhance thermodynamic favorability for specific enzymatic reactions.

Biosynthesis

Biological pathways

Flavin mononucleotide (FMN) is endogenously produced and metabolized in organisms through enzymatic pathways that ensure flavin cofactor . In animals, FMN synthesis relies on dietary uptake of , which serves as the direct precursor, whereas and can synthesize riboflavin de novo from (GTP) and ribulose 5-phosphate before converting it to FMN. This de novo pathway in prokaryotes involves a multi-step process encoded by the rib genes, such as ribA for GTP cyclohydrolase II, leading to riboflavin formation in a regulated manner. In , similar GTP-dependent synthesis occurs in plastids, with bifunctional enzymes like RIBA1 catalyzing initial steps, highlighting evolutionary conservation across these kingdoms. The core conversion of riboflavin to FMN is catalyzed by riboflavin kinase (RFK, EC 2.7.1.26), which phosphorylates riboflavin at the 5'-position using ATP as the phosphate donor:
Riboflavin+ATP→FMN+ADP\text{Riboflavin} + \text{ATP} \rightarrow \text{FMN} + \text{ADP}
This reaction is universal across organisms and often occurs via bifunctional RFK/FMN adenylyltransferase enzymes in prokaryotes, such as in Bacillus subtilis. FMN is then further processed to flavin adenine dinucleotide (FAD) by FAD pyrophosphorylase (also known as FMN adenylyltransferase, EC 2.7.7.2), which transfers an adenylyl group from ATP:
FMN+ATP→FAD+PPi\text{FMN} + \text{ATP} \rightarrow \text{FAD} + \text{PP}_\text{i}
In microbial systems, this step is tightly coupled to FMN production for efficient cofactor assembly, with overexpression of these enzymes enhancing yields in biotechnological strains. Biosynthesis is subject to feedback regulation to prevent overaccumulation of flavins. In bacteria like Corynebacterium ammoniagenes, RFK activity is inhibited by FMN and , with FMN acting as an uncompetitive inhibitor that modulates the rate based on cellular flavin levels. Similar inhibitory mechanisms operate in other prokaryotes, often integrated with transcriptional control via FMN-binding riboswitches that repress the rib operon. FMN metabolism also includes degradation pathways that recycle the cofactor. FMN is hydrolyzed to riboflavin by nonspecific phosphohydrolases, such as alkaline phosphatase (ALP), which cleaves the phosphate group extracellularly or in cellular compartments:
FMN+H2O→Riboflavin+Pi\text{FMN} + \text{H}_2\text{O} \rightarrow \text{Riboflavin} + \text{P}_\text{i}
This process, with a reported K_m of approximately 0.3 μM for human ALP, facilitates riboflavin salvage and uptake, particularly in nutrient-limited environments, and is mediated by ectoenzymes like CD73 in tandem with ALP for sequential FAD-to-FMN-to-riboflavin conversion. In mitochondria, additional pyrophosphatases contribute to flavin turnover, maintaining balanced pools.

Synthetic production

Flavin mononucleotide (FMN) is primarily synthesized through chemical of , the precursor vitamin B2, at the 5'-hydroxyl position of the ribityl chain. This process typically involves reacting with phosphorylating agents such as phosphorus oxychloride (POCl₃), often in the presence of partially hydrolyzed forms or ortho-phosphoric acid to control reactivity and improve selectivity. Yields of 60-70% are achievable, but the product often contains 20-30% flavin impurities, including di- or tri-phosphorylated byproducts and positional isomers, necessitating subsequent purification. Alternative chemical routes employ polyphosphoric acid as the phosphorylating agent under heating conditions, offering milder reaction profiles but similar impurity challenges. Enzymatic synthesis provides a more selective alternative, utilizing recombinant riboflavin kinase (RFK, EC 2.7.1.26) to catalyze the ATP-dependent of to FMN. Overexpression of RFK in hosts like or Candida famata enhances conversion efficiency, with integrated ATP regeneration systems—such as polyphosphate s or acetate / cascades—addressing the stoichiometric ATP consumption. For instance, modular pathway engineering in E. coli with optimized RFK variants and ATP recycling has achieved FMN titers of up to 1017 mg/L in fed-batch fermentation. These biocatalytic approaches yield high-purity FMN (>95%) while minimizing chemical waste, though scalability remains limited by stability and cofactor costs. Industrial production of FMN increasingly relies on microbial fermentation of riboflavin overproducers, followed by enzymatic or chemical phosphorylation. Engineered strains of Bacillus subtilis, known for robust riboflavin yields exceeding 15 g/L, serve as platforms where FMN accumulation is promoted by overexpressing RFK and disrupting downstream FMN adenylyltransferase to prevent conversion to FAD. Similarly, Candida famata variants with multi-copy FMN1 (RFK homolog) integrations produce FMN directly, reaching titers of 231 mg/L in a 1 L bioreactor under optimized conditions. These processes use glucose or whey-based media under controlled pH (6.5-7.0) and aeration, enabling cost-effective scaling while reducing reliance on chemical synthesis. Purification of synthetically produced FMN typically involves ion-exchange on strong anion exchangers like DEAE-Sepharose, exploiting FMN's negative charge at neutral for separation from unreacted and impurities. Elution with or gradients yields fractions >90% pure, followed by concentration and crystallization as the sodium salt from aqueous solutions to obtain stable, yellow needles suitable for commercial use. Recent advances post-2020 emphasize sustainable biotechnological routes to lower ATP dependency in enzymatic synthesis. A notable integrates microalgal-derived as a high-energy P-donor in RFK-catalyzed reactions, enabling one-pot FMN (and subsequent ) generation from with near-zero waste through algal of byproducts. This system achieves ~1 g/L FMN intermediates in 2 hours, enhancing economic viability for large-scale production.

Biological functions

Role in redox reactions

Flavin mononucleotide (FMN) serves as a in flavoproteins, which constitute approximately 1-3% of proteins encoded in prokaryotic and eukaryotic genomes, enabling these enzymes to participate in a wide array of processes essential for cellular . As a tightly bound cofactor, FMN is non-covalently or covalently attached to the protein scaffold, allowing it to cycle through its oxidized, semiquinone, and reduced states to facilitate without dissociating during . This integration positions FMN as a versatile mediator in both catabolic and anabolic pathways, where it supports the oxidation of substrates to generate or biosynthetic precursors. In reactions, FMN primarily facilitates (two-electron) transfers or radical (one-electron) mechanisms, accommodating the diverse potentials encountered in metabolic networks. For instance, in the mitochondrial , FMN acts as the initial in complex I (NADH:ubiquinone ), where it receives a from NADH to form FMNH₂, subsequently passing electrons sequentially through iron-sulfur clusters to ubiquinone while contributing to proton translocation across the . This role underscores FMN's importance in , linking substrate oxidation to ATP synthesis. Beyond energy , FMN enables photoreceptor functions in light-sensing proteins, particularly through its absorption of blue light (around 450 nm) in LOV (light, oxygen, or voltage) domains, which triggers conformational changes to initiate signaling cascades for and circadian regulation in organisms ranging from to . In the context of cellular stress, FMN-containing flavoproteins, such as flavodoxins, contribute to the response by scavenging and maintaining under conditions like exposure. During ischemia/, FMN dissociation from complex I exacerbates mitochondrial dysfunction and production, highlighting its involvement in mitigating or propagating oxidative damage in hypoxic tissues upon reoxygenation.

Involvement in specific enzymes

Flavin mononucleotide (FMN) serves as a critical in , also known as Complex I of the mitochondrial respiratory chain, where it functions as the primary from NADH. In this enzyme, present across eukaryotes including humans, FMN is non-covalently bound to the 51 kDa subunit and facilitates the initial step of , reducing FMN to FMNH₂ before passing electrons through iron-sulfur clusters to ubiquinone. This process is essential for proton pumping and ATP production, with Complex I containing one FMN per functional unit. The Old Yellow Enzyme (OYE) family represents another key class of FMN-dependent flavoproteins, primarily found in bacteria and yeast, where FMN enables the stereoselective reduction of α,β-unsaturated carbonyl compounds. In organisms like Bacillus subtilis, OYE homologs such as YqjM utilize FMN to detoxify xenobiotics, including trinitrotoluene (TNT), by catalyzing nitro group reduction and facilitating the breakdown of toxic aromatic compounds. The FMN cofactor in OYE adopts a characteristic (βα)₈ barrel fold, positioning the isoalloxazine ring for hydride transfer from NADPH, which underscores its role in environmental adaptation and bioremediation potential. In bacterial , FMN is integral to the reaction catalyzed by in marine bacteria such as Vibrio harveyi and Photobacterium phosphoreum. Reduced FMNH₂, generated by flavin reductases using NADH or NADPH, binds to the α-subunit of the heterodimeric , reacting with oxygen and a long-chain to produce blue-green light (λ_max ≈ 490 nm), oxidized FMN, and . This FMN-dependent monooxygenation exemplifies a natural light-emitting system, with the enzyme's stabilizing the excited-state intermediate for emission. While electron transfer flavoprotein () itself contains FAD as its prosthetic group and shuttles electrons from acyl-CoA dehydrogenases during human fatty acid β-oxidation, highlighting interconnected flavin cofactors in mitochondrial energy metabolism. In humans, disruptions in flavin can impair this process, but direct FMN binding occurs in Complex I for broader respiratory support. In bacteria, nitrate reductase enzymes incorporate an FMN domain to support by reducing to . For instance, in Azotobacter vinelandii, FMN stimulates the TPNH-linked activity, enhancing electron flow in anaerobic or microaerobic conditions for utilization. This FMN involvement ensures efficient nitrogen cycling across kingdoms.

Nutritional and medical aspects

Relation to riboflavin

Flavin mononucleotide (FMN) is the phosphorylated derivative of , also known as vitamin B2, an essential water-soluble nutrient that humans cannot synthesize and must obtain from the diet. serves as the precursor to FMN and (FAD), the two principal coenzymes involved in reactions, with FMN formed via ATP-dependent by kinase. As an active coenzyme form, FMN facilitates in various metabolic processes, underscoring riboflavin's critical role in cellular energy production and defense. Dietary sources of riboflavin are abundant in foods such as dairy products, eggs, lean meats, organ meats, green leafy vegetables, , and nuts, which provide the primarily in free or coenzyme-bound forms. The recommended dietary allowance (RDA) for is 1.3 mg per day for adult men and 1.1 mg per day for adult women, levels typically met through a balanced diet but potentially insufficient in populations with limited access to fortified foods or animal products. Upon ingestion, dietary FMN and are hydrolyzed in the to free prior to absorption, a process mediated by phosphatases and pyrophosphatases in the upper intestine, enabling uptake via specific riboflavin transporters in the . Historically, was first isolated and characterized between 1933 and 1935 by researchers including and Paul Karrer, with its essential nutritional role confirmed shortly thereafter; in 1935, work in Otto Warburg's laboratory, particularly by Hugo Theorell, identified FMN as the coenzyme component of the "yellow enzyme" (old yellow enzyme), establishing its biochemical significance. While both FMN and FAD derive from , FMN predominates in certain bacterial systems, such as in flavoproteins involved in electron transport chains and (e.g., bacterial ), whereas FAD is more ubiquitous in eukaryotic enzymes. This distinction highlights FMN's specialized role in prokaryotic metabolism, distinct from the broader distribution of FAD in higher organisms.

Therapeutic uses and deficiency

Flavin mononucleotide (FMN), the phosphorylated form of (vitamin B2), plays a critical role in addressing riboflavin deficiency, known as ariboflavinosis, which manifests through symptoms such as angular , cheilosis, , seborrheic around the nose and mouth, hyperemia and edema of the oral and pharyngeal mucous membranes, , and normocytic-normochromic . These symptoms arise from impaired flavin-dependent enzymes due to insufficient riboflavin availability, leading to reduced FMN and () levels essential for energy metabolism and reactions. Supplementation with , which is rapidly converted to FMN in the body, effectively restores cofactor levels and alleviates these symptoms in most cases, particularly when initiated early. Beyond deficiency correction, FMN-related therapies, often administered as riboflavin precursors, show promise in several clinical conditions. For migraine prophylaxis, high-dose supplementation at 400 mg per day for at least three months significantly reduces attack frequency, severity, and duration in adults, with efficacy comparable to some pharmacological agents like or sodium , and a favorable profile. In hyperhomocysteinemia, supplementation lowers plasma levels, particularly in individuals homozygous for the MTHFR 677TT genotype, by enhancing activity, which relies on FMN as a cofactor; this effect is observed at doses of 1.6 mg per day and supports cardiovascular risk reduction. Among chronic alcoholics, who frequently exhibit deficiency due to impaired absorption and increased utilization, supplementation prevents complications like and , with alcohol inhibiting FMN and FAD phosphatase activity exacerbating the shortfall. A notable advancement in FMN's therapeutic applications occurred in October 2025, when the U.S. Food and Drug Administration (FDA) approved Epioxa (riboflavin 5'-phosphate sodium, equivalent to FMN ophthalmic solution) in formulations of 0.239% and 0.177% for epithelium-on corneal collagen cross-linking in patients with progressive keratoconus aged 13 years and older. This incision-free procedure involves topical application of Epioxa followed by ultraviolet light A exposure and oxygen, strengthening corneal collagen without epithelial removal, thereby reducing procedural risks and recovery time compared to traditional methods. The approval addresses a key gap in non-invasive treatments for keratoconus, a condition affecting corneal structure and vision. Dosage and administration of FMN or vary by indication: oral riboflavin at 400 mg daily for prevention, divided doses for hyperhomocysteinemia or alcoholism-related deficiency, and specific ophthalmic instillation protocols for Epioxa (e.g., multiple drops over 20-30 minutes pre-UV exposure). Intravenous riboflavin may be used in severe deficiency cases for rapid repletion. Side effects are minimal, primarily limited to harmless yellow discoloration of or with high oral doses, and transient ocular with topical FMN; no serious adverse events are commonly reported at therapeutic levels.

Industrial and other applications

Food additive

Flavin mononucleotide, also known as riboflavin 5'-phosphate sodium, is approved for use as a under the designation E 101(ii). It functions primarily as an orange-red, water-soluble colorant, imparting a vibrant hue to various processed foods such as beverages, cereals, products, jellies, milk-based items, and sweets. This additive is particularly valued in formulations requiring stable pigmentation in aqueous environments, where its enhanced solubility compared to (E 101(i)) makes it suitable for liquid applications like drinks and . In addition to its coloring properties, flavin mononucleotide serves as a fortificant to restore or enhance vitamin B2 () levels in processed s, helping to compensate for losses during and supporting nutritional adequacy. The U.S. recognizes it as (GRAS) for use as a supplement in products, with no specified upper limits beyond good practices. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) has established a group (ADI) of "not specified" for and its derivatives, including riboflavin 5'-phosphate sodium, indicating low toxicity and no need for numerical restriction based on available data. The (EFSA) has similarly concluded that its use as a is unlikely to raise safety concerns at authorized levels, supported by toxicological studies showing no , carcinogenicity risks, or adverse effects in subchronic animal trials.

Biotechnology and research uses

In , flavin mononucleotide (FMN) serves as a key in light-sensitive domains derived from bacterial photoreceptors, enabling precise control of cellular processes through . For instance, FMN-binding proteins like those from the LOV (light oxygen voltage) domain family are engineered into synthetic circuits to act as blue-light sensors, facilitating programmable biosensors that detect environmental signals and trigger in living cells. These tools have been integrated into hydrogel-based platforms, known as OptoGels, which allow extracellular optogenetic modulation of cell behavior for applications in and . FMN-dependent enzymes play a prominent role in biocatalysis, particularly in green chemistry processes that achieve stereoselective reductions of activated alkenes to produce chiral compounds. Old Yellow Enzyme (OYE) homologs, which utilize FMN as a cofactor, catalyze asymmetric C=C bond reductions using NAD(P)H as the hydride donor, enabling the synthesis of enantiopure building blocks for pharmaceuticals with high efficiency and minimal environmental impact. These flavin-based ene-reductases have been applied in continuous-flow systems to scale up production of chiral intermediates, such as those used in drug synthesis, outperforming traditional chemical catalysts in terms of selectivity and sustainability. Recent advances include prenylated FMN (prFMN)-dependent UbiD-family enzymes, which catalyze reversible decarboxylations of aromatic acids, supporting the biotechnological production of biofuels like isobutene from renewable feedstocks as of 2021. As research tools, FMN facilitates advanced spectroscopic studies of flavoproteins, including fluorescent probes that exploit its intrinsic for real-time monitoring of protein dynamics. In (NMR) applications, 15N-labeled FMN enables sensitive detection of oxidized flavin intermediates and spin dynamics in active sites, providing insights into catalytic mechanisms without disrupting native structures. Additionally, 19F-substituted FMN analogs serve as probes in flavoprotein reconstitution experiments, allowing NMR analysis of cofactor-protein interactions and conformational changes during cycling. Emerging applications of FMN include its use in photodynamic therapy (PDT), where it acts as a non-toxic that generates upon blue-light irradiation to selectively target cancer cells. In models, FMN has demonstrated efficacy in PDT by inducing in tumor cells while sparing healthy tissue, leveraging its endogenous to minimize side effects. Furthermore, FMN-functionalized cerium fluoride nanoparticles enhance by combining properties for deep-tissue activation with targeted ROS production, enabling controlled release of therapeutics in hypoxic tumor environments. In industrial biotechnology, engineered microbial strains overproduce FMN as a cofactor for large-scale enzymatic processes, addressing supply demands for biocatalytic industries. strains with optimized biosynthesis pathways and overexpression of kinase achieve elevated FMN yields under controlled conditions, supporting cofactor recycling in multi-enzyme cascades for sustainable chemical manufacturing. of these strains, including pathway optimization and cofactor balancing, has increased FMN productivity by over 10-fold, facilitating its use in commercial reactions.

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