Editing Riboflavin (section)

==Synthesis==
===Biosynthesis===
Biosynthesis takes place in bacteria, fungi and plants, but not animals.<ref name=PKIN2020B2 /> The biosynthetic precursors to riboflavin are [[ribulose 5-phosphate]] and [[guanosine triphosphate]]. The former is converted to L-3,4-dihydroxy-2-butanone-4-phosphate. Guanosine is degraded to [[4-Hydroxy-2,4,5-triaminopyrimidine|4-hydroxy-2,4,5-triaminopyrimidine]], which is transformed into 5-amino-6-(D-ribitylamino)uracil. These two compounds are then the substrates for the penultimate step in the pathway, catalysed by the enzyme [[lumazine synthase]] in reaction {{EC number|2.5.1.78}}.<ref name=Bacher>{{cite journal |doi=10.1016/j.abb.2008.02.008  |title=Biosynthesis of vitamin B2: Structure and mechanism of riboflavin synthase |year=2008 |vauthors=Fischer M, Bacher A |journal=Archives of Biochemistry and Biophysics |volume=474 |issue=2 |pages=252–265 |pmid=18298940 }}</ref><ref name=Metacyc>{{cite web |url=https://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6168&detail-level=2 |title=Pathway: flavin biosynthesis III (fungi) |vauthors=Caspi R |publisher=MetaCyc Metabolic Pathway Database |date=2009-03-17 |access-date=2021-11-21 |archive-date=21 November 2021 |archive-url=https://web.archive.org/web/20211121162528/https://biocyc.org/META/NEW-IMAGE?type=PATHWAY&object=PWY-6168&detail-level=2 |url-status=live }}</ref><ref>{{Cite journal|vauthors=Wei Y, Kumar P, Wahome N, Mantis NJ, Middaugh CR|date=2018|title=Biomedical Applications of Lumazine Synthase|url=https://www.researchgate.net/publication/325109792|journal=Journal of Pharmaceutical Sciences|volume=107|issue=9|pages=2283–96|doi=10.1016/j.xphs.2018.05.002|pmid=29763607|s2cid=21729139|access-date=29 December 2021|archive-date=20 March 2024|archive-url=https://web.archive.org/web/20240320024255/https://www.researchgate.net/publication/325109792_Biomedical_Applications_of_Lumazine_Synthase|url-status=live}}</ref>
:[[File:Lumazine synthase reaction.svg|upright=2|class=skin-invert-image]]
In the final step of the biosynthesis, two molecules of [[6,7-dimethyl-8-ribityllumazine]] are combined by the enzyme [[riboflavin synthase]] in a [[dismutation]] reaction. This generates one molecule of riboflavin and one of 5-amino-6-(D-ribitylamino) uracil. The latter is recycled to the previous reaction in the sequence.<ref name=Bacher /><ref name=Metacyc />
:[[File:Riboflavin synthase dismutation.svg|upright=2|class=skin-invert-image]]
Conversions of riboflavin to the [[Cofactor (biochemistry)|cofactors]] FMN and FAD are carried out by the enzymes [[riboflavin kinase]] and [[FMN adenylyltransferase|FAD synthetase]] acting sequentially.<ref name=Metacyc /><ref>{{cite book | vauthors = Devlin TM | title = Textbook of Biochemistry: with Clinical Correlations | date = 2011 | publisher = John Wiley & Sons | location = Hoboken, NJ | isbn = 978-0-470-28173-4 | edition = 7th }}</ref>
:[[File:FAD Synthesis.png|thumb|class=skin-invert-image|Riboflavin is the biosynthetic precursor of FMN and FAD]]

===Industrial synthesis===
[[File:Micrococcus riboflavin.jpg|thumb|Cultures of ''Micrococcus luteus'' growing on pyridine (left) and succinic acid (right). The pyridine culture has turned yellow from the accumulation of riboflavin.<ref name="Sims1992"/>]]
The industrial-scale production of riboflavin uses various microorganisms, including [[Mold (fungus)|filamentous fungi]] such as ''[[Ashbya gossypii]]'', ''[[Candida famata]]'' and ''Candida flaveri'',  as well as the [[bacteria]] ''[[Corynebacterium]] ammoniagenes'' and ''[[Bacillus subtilis]]''. ''B. subtilis'' that has been genetically modified to both increase the production of riboflavin and to introduce an antibiotic ([[ampicillin]]) resistance marker, is employed at a commercial scale to produce riboflavin for [[animal feed|feed]] and food fortification.<ref name=Stahmann>{{cite journal | vauthors = Stahmann KP, Revuelta JL, Seulberger H | title = Three biotechnical processes using Ashbya gossypii, Candida famata, or Bacillus subtilis compete with chemical riboflavin production | journal = Applied Microbiology and Biotechnology | volume = 53 | issue = 5 | pages = 509–16 | date = May 2000 | pmid = 10855708 | doi = 10.1007/s002530051649 | s2cid = 2471994 }}</ref> By 2012, over 4,000 tonnes per annum were produced by such fermentation processes.<ref name=Anie>{{cite journal | vauthors = Eggersdorfer M, Laudert D, Létinois U, McClymont T, Medlock J, Netscher T, Bonrath W | title = One hundred years of vitamins-a success story of the natural sciences | journal = Angewandte Chemie | volume = 51 | issue = 52 | pages = 12960–12990 | date = December 2012 | pmid = 23208776 | doi = 10.1002/anie.201205886 }}</ref>

In the presence of high concentrations of hydrocarbons or aromatic compounds, some bacteria overproduce riboflavin, possibly as a protective mechanism. One such organism is ''[[Micrococcus luteus]]'' ([[American Type Culture Collection]] 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.<ref name="Sims1992">{{cite journal | vauthors = Sims GK, O'loughlin EJ | title = Riboflavin Production during Growth of Micrococcus luteus on Pyridine | journal = Applied and Environmental Microbiology | volume = 58 | issue = 10 | pages = 3423–5 | date = October 1992 | pmid = 16348793 | pmc = 183117 | doi = 10.1128/AEM.58.10.3423-3425.1992 | bibcode = 1992ApEnM..58.3423S }}</ref>

===Laboratory synthesis===
The first [[total synthesis]] of riboflavin was carried out by [[Richard Kuhn]]'s group.<ref name=Anie/><ref>{{cite journal |doi=10.1002/cber.19350680922 |title=Über die Synthese des Lactoflavins (Vitamin B 2 ) |year=1935 | vauthors = Kuhn R, Reinemund K, Weygand F, Ströbele R |journal=Berichte der Deutschen Chemischen Gesellschaft (A and B Series) |volume=68 |issue=9 |pages=1765–1774|language=de }}</ref> A substituted [[aniline]], produced by [[reductive amination]] using [[D-ribose]], was [[condensation reaction|condensed]] with [[alloxan]] in the final step:
:[[File:Riboflavin synthesis.svg|upright=2|class=skin-invert-image]]