Riboflavin - AbsoluteAstronomy.com

Riboflavin, also known as vitamin B₂ or additive
E number
E numbers are number codes for food additives that have been assessed for use within the European Union . They are commonly found on food labels throughout the European Union. Safety assessment and approval are the responsibility of the European Food Safety Authority...

E101, is an easily absorbed micronutrient

Micronutrient

Micronutrients are nutrients required by humans and other living things throughout life in small quantities to orchestrate a whole range of physiological functions, but which the organism itself cannot produce. For people, they include dietary trace minerals in amounts generally less than 100...

with a key role in maintaining health

Health

Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain...

in humans and animals. It is the central component of the cofactor

Cofactor (biochemistry)

A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....

s FAD

FAD

In biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety bound to the phosphate...

and FMN

Flavin mononucleotide

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...

, and is therefore required by all flavoprotein

Flavoprotein

Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: the flavin adenine dinucleotide or flavin mononucleotide ....

s. As such, vitamin B₂ is required for a wide variety of cellular processes. It plays a key role in energy metabolism, and for the metabolism

Metabolism

Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

of fat

Fat

Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...

s, ketone bodies

Ketone bodies

Ketone bodies are three water-soluble compounds that are produced as by-products when fatty acids are broken down for energy in the liver and kidney. They are used as a source of energy in the heart and brain. In the brain, they are a vital source of energy during fasting...

, carbohydrate

Carbohydrate

A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...

s, and proteins.

Milk

Milk

Milk is a white liquid produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals before they are able to digest other types of food. Early-lactation milk contains colostrum, which carries the mother's antibodies to the baby and can reduce the risk of many...

, cheese

Cheese

Cheese is a generic term for a diverse group of milk-based food products. Cheese is produced throughout the world in wide-ranging flavors, textures, and forms....

, leafy green vegetables, liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, kidney

Kidney

The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

s, legumes, tomatoes, yeast

Yeast

Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...

, mushrooms, and almond

Almond

The almond , is a species of tree native to the Middle East and South Asia. Almond is also the name of the edible and widely cultivated seed of this tree...

s are good sources of vitamin B₂, but exposure to light destroys riboflavin.

The name "riboflavin" comes from "ribose

Ribose

Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....

" (the sugar whose reduced form, ribitol

Ribitol

Ribitol or adonitol is a crystalline pentose alcohol formed by the reduction of ribose. It occurs naturally in the plant Adonis vernalis, as well as in the cell walls of Gram positive bacteria . It also contributes to the chemical structure of riboflavin.-External links:**...

, forms part of its structure) and "flavin", the ring-moiety which imparts the yellow color to the oxidized molecule (from Latin flavus, "yellow"). The reduced form, which occurs in metabolism along with the oxidized form, is colorless.

Riboflavin is best known visually as the vitamin which imparts the orange color to solid B-vitamin preparations, the yellow color to vitamin supplement solutions, and the unusual fluorescent-yellow color to the urine of persons who supplement with high-dose B-complex preparations (no other vitamin imparts any color to urine).

Discovery

Vitamin B was originally considered to have two components, a heat-labile vitamin B₁ and a heat-stable vitamin B₂. In the 1920s, vitamin B₂ was thought to be the factor necessary for preventing pellagra

Pellagra

Pellagra is a vitamin deficiency disease most commonly caused by a chronic lack of niacin in the diet. It can be caused by decreased intake of niacin or tryptophan, and possibly by excessive intake of leucine. It may also result from alterations in protein metabolism in disorders such as carcinoid...

. In 1923, Paul Gyorgy in Heidelberg was investigating egg white injury in rats; the curative factor for this condition was called vitamin H. Since both pellagra and vitamin H deficiency were associated with dermatitis, Gyorgy decided to test the effect of vitamin B₂ on vitamin H deficiency in rats. He enlisted the service of Wagner-Jauregg in Kuhn’s laboratory. In 1933, Kuhn, Gyorgy, and Wagner found that thiamin-free extracts of yeast, liver, or rice bran prevented the growth failure of rats fed a thiamin-supplemented diet.

Further, they noted that a yellow-green fluorescence in each extract promoted rat growth, and that the intensity of fluorescence was proportional to the effect on growth. This observation enabled them to develop a rapid chemical and bioassay to isolate the factor from egg white in 1933, they called it Ovoflavin. The same group then isolated the same preparation (a growth-promoting compound with yellow-green fluorescence) from whey using the same procedure (lactoflavin). In 1934 Kuhn’s group identified the structure of so-called flavin and synthesized vitamin B₂.

Biochemical function

Flavin mononucleotide

(FMN) and flavin adenine dinucleotide (FAD) function as coenzymes for a wide variety of oxidative enzymes and remain bound to the enzymes during the oxidation-reduction reactions. Flavins can act as oxidizing agents because of their ability to accept a pair of hydrogen atoms. Reduction of isoalloxazine ring (FAD, FMN oxidized form) yields the reduced forms of the flavoproteins (FMNH2 and FADH2).

Mechanism of action as cofactors and flavoproteins

Flavoproteins exhibit a wide range of redox potential and therefore can play a wide variety of roles in intermediary metabolism. Some of these roles are:

Flavoproteins play very important roles in the electron transport chain
Decarboxylation of pyruvate and α-ketoglutarate requires FAD
Fatty acyl CoA dehydrogenase requires FAD in fatty acid oxidation
FAD is required to the production of pyridoxic acid from pyridoxal (vitamin B₆)
The primary coenzyme form of vitamin B₆ (pyridoxal phosphate) is FMN dependent
FAD is required to convert retinal (vitamin A) to retinoic acid
Synthesis of an active form of folate (5-methyl THF) is FADH2 dependent
FAD is required to convert tryptophan to niacin (vitamin B₃)
Reduction of the oxidized form of glutathione (GSSG) to its reduced form (GSH) is also FAD dependent

Riboflavin in food: occurrence, sources and stability

Riboflavin is yellow or yellow-orange in color and in addition to being used as a food coloring

Food coloring

Food coloring is a substance, liquid or powder, that is added to food or drink to change its color. Food coloring is used both in commercial food production and in domestic cooking...

, it is also used to fortify some foods. It is used in baby food

Baby food

Baby food is any food, other than breastmilk or infant formula, that is made specifically for infants, roughly between the ages of four to six months to 2 years. The food comes in multiple varieties and tastes, can be produced by many manufacturers, or may be table food that the rest of the family...

s, breakfast cereal

Breakfast cereal

A breakfast cereal is a food made from processed grains that is often, but not always, eaten with the first meal of the day. It is often eaten cold, usually mixed with milk , water, or yogurt, and sometimes fruit but sometimes eaten dry. Some cereals, such as oatmeal, may be served hot as porridge...

s, pasta

Pasta

Pasta is a staple food of traditional Italian cuisine, now of worldwide renown. It takes the form of unleavened dough, made in Italy, mostly of durum wheat , water and sometimes eggs. Pasta comes in a variety of different shapes that serve for both decoration and to act as a carrier for the...

s, sauce

Sauce

In cooking, a sauce is liquid, creaming or semi-solid food served on or used in preparing other foods. Sauces are not normally consumed by themselves; they add flavor, moisture, and visual appeal to another dish. Sauce is a French word taken from the Latin salsus, meaning salted...

s, processed cheese

Processed cheese

Processed cheese, process cheese, cheese slice, prepared cheese, cheese singles or cheese food is a food product made from normal cheese and sometimes other unfermented dairy ingredients, plus emulsifiers, extra salt, food colorings, or whey...

, fruit drinks, vitamin-enriched milk products, and some energy drink

Energy drink

Energy drinks are beverages whose producers advertise that they "boost energy." These advertisements usually do not emphasize energy derived from the sugar and caffeine they contain but rather increased energy release due to a variety of stimulants and vitamins....

s. Regarding occurrence and sources of vitamin B₂, yeast extract is considered to be exceptionally rich in vitamin B₂, and liver and kidney are also rich sources. Wheat bran, eggs, meat, milk, and cheese are important sources in diets containing these foods. Cereals grains contain relatively low concentrations of flavins, but are important sources in those parts of the world where cereals constitute the staple diet. The milling of cereals results in considerable loss (up to 60%) of vitamin B₂, so white flour is enriched in some countries such as USA by addition of the vitamin. The enrichment of bread and ready-to-eat breakfast cereals contributes significantly to the dietary supply of vitamin B₂. Polished rice is not usually enriched, because the vitamin’s yellow color would make the rice visually unacceptable to the major rice-consumption populations. However, most of the flavins content of the whole brown rice is retained if the rice is steamed prior to milling. This process drives the flavins in the germ and aleurone layers into the endosperm. Free riboflavin is naturally present in foods along with protein-bound FMN and FAD. Bovine milk contains mainly free riboflavin, with a minor contribution from FMN and FAD. In whole milk, 14% of the flavins are bound noncovalently to specific proteins. Egg white and egg yolk contain specialized riboflavin-binding proteins, which are required for storage of free riboflavin in the egg for use by the developing embryo.

It is difficult to incorporate riboflavin into many liquid products because it has poor solubility in water, hence the requirement for riboflavin-5'-phosphate (E101a

E number

E numbers are number codes for food additives that have been assessed for use within the European Union . They are commonly found on food labels throughout the European Union. Safety assessment and approval are the responsibility of the European Food Safety Authority...

), a more expensive but more soluble form of riboflavin.

Riboflavin is generally stable during the heat processing and normal cooking of foods if light is excluded. The alkaline conditions in which riboflavin is unstable are rarely encountered in foodstuffs. Riboflavin degradation in milk can occur slowly in dark during storage in the refrigerator.
(7).

Recommended dietary allowance (RDA)

The latest (1998) RDA recommendations for vitamin B₂ are similar to the 1989 RDA, which for adults, suggested a minimum intake of 1.2 mg for persons whose caloric intake may be > 2,000 Kcal. The current RDAs for riboflavin for adult men and women are 1.3 mg/day and 1.1 mg/day, respectively; the estimated average requirement for adult men and women are 1.1 mg and 0.9 mg, respectively. Recommendations for daily riboflavin intake increase with pregnancy and lactation to 1.4 mg and 1.6 mg, respectively (1in advanced). For infants, the RDA is 0.3-0.4 mg/day and for children it is 0.6-0.9 mg/day.

Riboflavin deficiency

Riboflavin is continuously excreted in the urine of healthy individuals, making deficiency relatively common when dietary intake is insufficient. However, riboflavin deficiency is always accompanied by deficiency of other vitamins.

A deficiency of riboflavin can be primary - poor vitamin sources in one's daily diet - or secondary, which may be a result of conditions that affect absorption in the intestine, the body not being able to use the vitamin, or an increase in the excretion of the vitamin from the body.

In humans, signs and symptoms of riboflavin deficiency (ariboflavinosis

Ariboflavinosis

Ariboflavinosis is the medical condition caused by deficiency of riboflavin . Ariboflavinosis is most often seen in association with protein-energy malnutrition, and also in cases of alcoholism....

) include cracked and red lips, inflammation of the lining of mouth and tongue, mouth ulcers, cracks at the corners of the mouth (angular cheilitis

Angular cheilitis

Angular cheilitis is an inflammatory lesion at the labial commissure, or corner of the mouth, and often occurs bilaterally. The condition manifests as deep cracks or splits...

), and a sore throat. A deficiency may also cause dry and scaling skin, fluid in the mucous membranes, and iron-deficiency anemia. The eyes may also become bloodshot, itchy, watery and sensitive to bright light.

Riboflavin deficiency is classically associated with the oral-ocular-genital syndrome. Angular cheilitis, photophobia, and scrotal dermatitis are the classic remembered signs.

In animals, riboflavin deficiency results in lack of growth, failure to thrive, and eventual death. Experimental riboflavin deficiency in dogs results in growth failure, weakness, ataxia, and inability to stand. The animals collapse, become comatose, and die. During the deficiency state, dermatitis develops together with hair loss. Other signs include corneal opacity, lenticular cataracts, hemorrhagic adrenals, fatty degeneration of the kidney and liver, and inflammation of the mucous membrane of the gastrointestinal tract. Post-mortem studies in rhesus monkeys fed a riboflavin-deficient diet revealed about one-third the normal amount of riboflavin was present in the liver, which is the main storage organ for riboflavin in mammals. These overt clinical signs of riboflavin deficiency are rarely seen among inhabitants of the developed countries. However, about 28 million Americans exhibit a common ‘sub-clinical’ stage. characterized by a change in biochemical indices (e.g. reduced plasma erythrocyte glutathione reductase levels). Although the effects of long-term subclinical riboflavin deficiency are unknown, in children this deficiency results in reduced growth. Subclinical riboflavin deficiency has also been observed in women taking oral contraceptives, in the elderly, in people with eating disorders, and in disease states such as HIV, inflammatory bowel disease, diabetes and chronic heart disease. The fact that riboflavin deficiency does not immediately lead to gross clinical manifestations indicates that the systemic levels of this essential vitamin are tightly regulated.

Assessment of riboflavin status

Biochemical tests are essential for confirming clinical cases of riboflavin deficiency and for establishing subclinical deficiencies. Among these tests:

Erythrocyte glutathione reductase activity:

Glutathione reductase

Glutathione reductase, also known as GSR or GR, is an enzyme that reduces glutathione disulfide to the sulfhydryl form GSH, which is an important cellular antioxidant....

is a nicotinamide adenine dinucleotide phosphate (NADPH), a FAD-dependent enzyme, and the major flavoproteins in erythrocyte. The measurement of the activity coefficient of erythrocyte glutathione reductase (EGR) is the preferred method for assessing riboflavin status. It provides a measure of tissue saturation and long-term riboflavin status. In vitro enzyme activity in terms of activity coefficients (AC) is determined both with and without the addition of FAD to the medium. ACs represent a ratio of the enzyme’s activity with FAD to the enzyme’s activity without FAD. An AC of 1.2 to 1.4, riboflavin status is considered low when FAD is added to stimulate enzyme activity. An AC > 1.4 suggests riboflavin deficiency. On the other hand, if FAD is added and AC is < 1.2, then riboflavin status is considered acceptable. Tillotson and Bashor reported that a decrease in the intakes of riboflavin was associated with increase in EGR AC. In the U.K. study of Norwich elderly, initial EGR AC values for both males and females were significantly correlated with those measured 2 years later, suggesting that EGR AC may be a reliable measure of long-term biochemical riboflavin status of individuals. These findings are consistent with earlier studies.

Urinary riboflavin excretion:

Experimental balance studies indicate that urinary riboflavin excretion rates increase slowly with increasing intakes, until intake level approach 1.0 mg/d, when tissue saturation occurs. At higher intakes, the rate of excretion increases dramatically. Once intakes of 2.5 mg/d are reached, excretion becomes approximately equal to the rate of absorption (Horwitt et al., 1950)(18). At such high intake a significant proportion of the riboflavin intake is not absorbed.If urinary riboflavin excretion is <19 µg/g creatinine (without recent riboflavin intake) or < 40 µg per day are indicative of deficiency.

Clinical uses

Riboflavin has been used in several clinical and therapeutic situations. For over 30 years, riboflavin supplements have been used as part of the phototherapy treatment of neonatal jaundice

Neonatal jaundice

Neonatal jaundice or Neonatal hyperbilirubinemia is a yellowing of the skin and other tissues of a newborn infant. A bilirubin level of more than 85 umol/l manifests clinical jaundice in neonates whereas in adults a level of 34 umol/l would look icteric...

. The light used to irradiate the infants breaks down not only bilirubin

Bilirubin

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...

, the toxin causing the jaundice, but also the naturally occurring riboflavin within the infant's blood, so extra supplementation is necessary.

High dose riboflavin appears to be useful alone or along with beta-blockers in the prevention of migraine

Migraine

Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...

. A dose of 400 mg daily has been used effectively in the prophylaxis of migraines, especially in combination with a daily supplement of magnesium citrate

Magnesium citrate

Magnesium citrate, a magnesium salt of citric acid, is a chemical agent used medicinally as a saline laxative and to completely empty the bowel prior to a major surgery or colonoscopy. It is available without a prescription, both as a generic brand or under the brand name Citromag or Citroma. It is...

500 mg and, in some cases, a supplement of coenzyme Q10.

Riboflavin has also been used as a muscle pain reliever.

Riboflavin in combination with UV light has been shown to be effective in reducing the ability of harmful pathogens found in blood products to cause disease. When UV light is applied to blood products containing riboflavin, the nucleic acids in pathogens are damaged, rendering them unable to replicate and cause disease. Riboflavin and UV light treatment

Pathogen reduction using riboflavin and UV light

Pathogen reduction using riboflavin and UV light is a method by which infectious pathogens in blood for transfusion are inactivated by adding riboflavin and irradiating with UV light. This method reduces the infectious levels of disease-causing agents that may be found in donated blood components,...

has been shown to be effective for inactivating pathogens in platelets and plasma, and is under development for application to whole blood. Because platelets and red blood cells do not contain a nucleus (i.e. they have no DNA to be damaged) the technique is well-suited for destroying nucleic acid containing pathogens (including viruses, bacteria, parasites, and white blood cells) in blood products.

Recently, riboflavin has been used in a new treatment to slow or stop the progression of the corneal disorder keratoconus

Keratoconus

Keratoconus , is a degenerative disorder of the eye in which structural changes within the cornea cause it to thin and change to a more conical shape than its normal gradual curve....

. This is called corneal collagen crosslinking (CXL). In corneal crosslinking, riboflavin drops are applied to the patient’s corneal surface. Once the riboflavin has penetrated through the cornea, ultraviolet A light therapy is applied. This induces collagen crosslinking, which increases the tensile strength of the cornea. The treatment has been shown in several studies to stabilize keratoconus.

Industrial uses

Because riboflavin is fluorescent

Fluorescence

Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation of a different wavelength. It is a form of luminescence. In most cases, emitted light has a longer wavelength, and therefore lower energy, than the absorbed radiation...

under UV light

Ultraviolet

Ultraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...

, dilute solutions (0.015-0.025% w/w) are often used to detect leaks or to demonstrate coverage in an industrial system such a chemical blend tank or bioreactor. (See the ASME BPE

ASME BPE

ASME BPE is the Bioprocess Equipment group of the ASME that provides engineers and quality control professionals a measurable way to specify and purchase equipment for the Biotechnology, Pharmaceutical and Personal Care Products industries.- Latest news :...

section on Testing and Inspection for additional details.)

Good sources

Riboflavin is found naturally in asparagus

Asparagus

Asparagus officinalis is a spring vegetable, a flowering perennialplant species in the genus Asparagus. It was once classified in the lily family, like its Allium cousins, onions and garlic, but the Liliaceae have been split and the onion-like plants are now in the family Amaryllidaceae and...

, popcorn

Popcorn

Popcorn, or popping corn, is corn which expands from the kernel and puffs up when heated. Corn is able to pop because, like sorghum, quinoa and millet, its kernels have a hard moisture-sealed hull and a dense starchy interior. This allows pressure to build inside the kernel until an explosive...

, bananas, persimmons, okra

Okra

Okra is a flowering plant in the mallow family. It is valued for its edible green seed pods. The geographical origin of okra is disputed, with supporters of South Asian, Ethiopian and West African origins...

, chard

Chard

Chard , is a leafy green vegetable often used in Mediterranean cooking. While the leaves are always green, chard stalks vary in color. Chard has been bred to have highly nutrious leaves at the expense of the root...

, cottage cheese

Cottage cheese

Cottage cheese is a cheese curd product with a mild flavor. It is drained, but not pressed, so some whey remains and the individual curds remain loose. The curd is usually washed to remove acidity, giving sweet curd cheese. It is not aged or colored. Different styles of cottage cheese are made from...

, milk

Milk

, yogurt, meat

Meat

Meat is animal flesh that is used as food. Most often, this means the skeletal muscle and associated fat and other tissues, but it may also describe other edible tissues such as organs and offal...

, eggs

Egg (food)

Eggs are laid by females of many different species, including birds, reptiles, amphibians, and fish, and have probably been eaten by mankind for millennia. Bird and reptile eggs consist of a protective eggshell, albumen , and vitellus , contained within various thin membranes...

, fish

Fish (food)

Fish is a food consumed by many species, including humans. The word "fish" refers to both the animal and to the food prepared from it. Fish has been an important source of protein for humans throughout recorded history.-Terminology:...

, and green bean

Green bean

Green beans , also known as French beans , are the unripe fruit of any kind of bean, including the yardlong bean, the hyacinth bean, the winged bean, and especially the common bean , whose pods are also usually called string beans in the northeastern and western United States, but can also be...

s (particularly on the ends), each of which contain at least 0.1 mg of the vitamin per 3–10.5 oz (85–297.7 g) serving.(5). Other sources specify cheese

Cheese

Cheese is a generic term for a diverse group of milk-based food products. Cheese is produced throughout the world in wide-ranging flavors, textures, and forms....

, leafy green vegetables, liver

Liver

, kidney

Kidney

s, legumes, tomatoes, yeast

Yeast

, mushrooms, and almond

Almond

The almond , is a species of tree native to the Middle East and South Asia. Almond is also the name of the edible and widely cultivated seed of this tree...

s.

Riboflavin is destroyed by exposure to ultraviolet light, so milk sold in transparent (glass/plastic) bottles will likely contain less riboflavin than milk sold in opaque containers.

Toxicity

Riboflavin is not toxic when taken orally, as its low solubility keeps it from being absorbed in dangerous amounts within the digestive tract. Although toxic doses can be administered by injection, any excess at nutritionally relevant doses is excreted in the urine, imparting a bright yellow color when in large quantities.
In humans, there is no evidence for riboflavin toxicity produced by excessive intakes, though it helps relieve muscle pain. Even when 400 mg/d of riboflavin was given orally to subjects in one study for three months to investigate the efficacy of riboflavin in the prevention of migraine headache, no short-term side effects were reported.

Industrial synthesis

Various biotechnological processes have been developed for industrial scale riboflavin biosynthesis using different microorganisms, including filamentous fungi

Mold

Molds are fungi that grow in the form of multicellular filaments called hyphae. Molds are not considered to be microbes but microscopic fungi that grow as single cells called yeasts...

such as Ashbya gossypii
Ashbya gossypii
Ashbya gossypii is a filamentous fungus or mold closely related to yeast, but growing exclusively in a filamentous way. It was originally isolated from cotton as a pathogen causing stigmatomycosis by Ashby and Novell in 1926...

, Candida famata and Candida flaveri, as well as the bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

Corynebacterium
Corynebacterium
Corynebacterium is a genus of Gram-positive rod-shaped bacteria. They are widely distributed in nature and are mostly innocuous. Some are useful in industrial settings such as C. glutamicum. Others can cause human disease. C...

ammoniagenes and Bacillus subtilis
Bacillus subtilis
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...

. The latter organism has been genetically modified to both increase the bacteria's production of riboflavin and to introduce an antibiotic (ampicillin

Ampicillin

Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...

) resistance marker, and is now successfully employed at a commercial scale to produce riboflavin for feed and food fortification purposes. The chemical company BASF

BASF

BASF SE is the largest chemical company in the world and is headquartered in Germany. BASF originally stood for Badische Anilin- und Soda-Fabrik . Today, the four letters are a registered trademark and the company is listed on the Frankfurt Stock Exchange, London Stock Exchange, and Zurich Stock...

has installed a plant in South Korea

South Korea

The Republic of Korea , , is a sovereign state in East Asia, located on the southern portion of the Korean Peninsula. It is neighbored by the People's Republic of China to the west, Japan to the east, North Korea to the north, and the East China Sea and Republic of China to the south...

, which is specialized on riboflavin production using Ashbya gossypii. The concentrations of riboflavin in their modified strain

Strain (biology)

In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

are so high, that the mycelium

Mycelium

thumb|right|Fungal myceliaMycelium is the vegetative part of a fungus, consisting of a mass of branching, thread-like hyphae. The mass of hyphae is sometimes called shiro, especially within the fairy ring fungi. Fungal colonies composed of mycelia are found in soil and on or within many other...

has a reddish / brownish color and accumulates riboflavin crystals in the vacuoles, which will eventually burst the mycelium. Riboflavin is sometimes overproduced, possibly as a protective mechanism, by certain bacteria in the presence of high concentrations of hydrocarbons or aromatic compounds. One such organism is Micrococcus luteus ( American Type Culture Collection

American Type Culture Collection

The American Type Culture Collection is a private, not-for-profit biological resource center whose mission focuses on the acquisition, authentication, production, preservation, development and distribution of standard reference microorganisms, cell lines and other materials for research in the...

strain number ATCC 49442), which develops a yellow color due to production of riboflavin while growing on pyridine, but not when grown on other substrates, such as succinic acid.