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Biotechnology of riboflavin

Applied Microbiology and Biotechnology volume 100, pages 2107–2119 (2016)Cite this article

Abstract

Riboflavin (vitamin B2) production has shifted from chemical synthesis to exclusive biotechnological synthesis in less than 15 years. The underlying extraordinary achievement in metabolic engineering and bioprocess engineering is reviewed in this article with regard to the two most important industrial producers Bacillus subtilis and Ashbya gossypii. The respective biosynthetic routes and modifications are discussed, and also the regulation of riboflavin synthesis. As the terminal biosynthesis of riboflavin starts from the two precursors, ribulose 5-phosphate and guanosine triphosphate (GTP), both strains have been optimized for an improved flux through the pentose phosphate pathway as well as the purine biosynthetic pathway. Specific targets for improvement of A. gossypii were the increase of the glycine pool and the increase of carbon flow through the glyoxylic shunt. In B. subtilis, research interest, amongst others, has focused on gluconeogenesis and overexpression of the rib operon. In addition, insight into large-scale production of vitamin B2 is given, as well as future prospects and possible developments.

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References

  • Abbas CA, Sibirny AA (2011) Genetic control of biosynthesis and transport of riboflavin and flavin nucleotides and construction of robust biotechnological producers. Microbiol Mol Biol Rev 75(2):321–360

    PubMed Central  Article  PubMed  CAS  Google Scholar 

  • Bacher A, Eberhardt S, Fischer M, Kis K, Richter G (2000) Biosynthesis of vitamin B2 (riboflavin). Annu Rev Nutr 20:153–167

    Article  PubMed  CAS  Google Scholar 

  • Banerjee R, Batschauer A (2005) Plant blue-light receptors. Planta 220(3):498–502

    Article  PubMed  CAS  Google Scholar 

  • Barbau-Piednoir E, De Keersmaecker SCJ, Wuyts V, Gau C, Pirovano W, Costessi A, Philipp P, Roosens NH (2015) Genome sequence of EU-unauthorized genetically modified Bacillus subtilis strain 2014–3557 overproducing riboflavin, isolated from a vitamin B2 80% feed additive. Genome Announc 3(2)

  • Becker J, Wittmann C (2012) Systems and synthetic metabolic engineering for amino acid production—the heartbeat of industrial strain development. Curr Opin Biotechnol 23(5):718–726

    Article  PubMed  CAS  Google Scholar 

  • Becker J, Zelder O, Häfner S, Schröder H, Wittmann C (2011) From zero to hero—design-based systems metabolic engineering of Corynebacterium glutamicum for l-lysine production. Metab Eng 13(2):159–168

    Article  PubMed  CAS  Google Scholar 

  • Bretzel W, Schurter W, Ludwig B, Kupfer E, Doswald S, Pfister M, van Loon A (1999) Commercial riboflavin production by recombinant Bacillus subtilis: down-stream processing and comparison of the composition of riboflavin produced by fermentation or chemical synthesis. J Ind Microbiol Biotechnol 22(1):19–26

    Article  CAS  Google Scholar 

  • Buey RM, Ledesma-Amaro R, Balsera M, de Pereda JM, Revuelta JL (2015) Increased riboflavin production by manipulation of inosine 5′-monophosphate dehydrogenase in Ashbya gossypii. Appl Microbiol Biotechnol 99(22):9577–9589

    Article  PubMed  CAS  Google Scholar 

  • Capozzi V, Menga V, Digesu AM, De Vita P, van Sinderen D, Cattivelli L, Fares C, Spano G (2011) Biotechnological production of vitamin B2-enriched bread and pasta. J Agric Food Chem 59(14):8013–8020

    Article  PubMed  CAS  Google Scholar 

  • Coquard D, Huecas M, Ott M, vanDijl JM, VanLoon A, Hohmann HP (1997) Molecular cloning and characterisation of the ribC gene from Bacillus subtilis: a point mutation in ribC results in riboflavin overproduction. Mol Gen Genet 254(1):81–84

    Article  PubMed  CAS  Google Scholar 

  • Demain AL (1972) Riboflavin oversynthesis. Annu Rev Microbiol 26:369

    Article  PubMed  CAS  Google Scholar 

  • Dmytruk K, Lyzak O, Yatsyshyn V, Kluz M, Sibirny V, Puchalski C, Sibirny A (2014) Construction and fed-batch cultivation of Candida famata with enhanced riboflavin production. J Biotechnol 172:11–17

    Article  PubMed  CAS  Google Scholar 

  • DSM (2006) Fermentative preparation of riboflavin involving recycling of lysed biomass as nutrient medium. Patent EP 1 731 617 A1, 13 Dec 2006

  • DSM (2015) DSM in Grenzach - Historie. http://www.dsm.com/countrysites/grenzach/de_DE/dsm-grenzach/historie.html. Accessed 05.10. 2015

  • Duan YX, Chen T, Chen X, Zhao XM (2010) Overexpression of glucose-6-phosphate dehydrogenase enhances riboflavin production in Bacillus subtilis. Appl Microbiol Biotechnol 85(6):1907–1914

    Article  PubMed  CAS  Google Scholar 

  • Eggersdorfer M, Laudert D, Létinois U, McClymont T, Medlock J, Netscher T, Bonrath W (2012) One hundred years of vitamins—a success story of the natural sciences. Angew Chem Int Ed Engl 51(52):12960–12990

    Article  PubMed  CAS  Google Scholar 

  • Fischer M, Bacher A (2005) Biosynthesis of flavocoenzymes. Nat Prod Rep 22(3):324–350

    Article  PubMed  CAS  Google Scholar 

  • Food and Nutrition Board (1998) Riboflavin. Dietary reference intakes: thiamin, riboflavin, niacin, vitamin B6, vitamin B12, pantothenic acid, biotin, folate and choline. The National Academies Press, Washington

    Google Scholar 

  • Förster C, Santos MA, Ruffert S, Krämer R, Revuelta JL (1999) Physiological consequence of disruption of the VMA1 gene in the riboflavin overproducer Ashbya gossypii. J Biol Chem 274(14):9442–9448

    Article  PubMed  Google Scholar 

  • Grimmer J, Kiefer H, Martin C (1993) Method of purifying ferment-produced riboflavin. Patent US 5,210,023 A, 01 July 1991

  • Gutiérrez-Preciado A, Torres AG, Merino E, Bonomi HR, Goldbaum FA, García-Angulo VA (2015) Extensive identification of bacterial riboflavin transporters and their distribution across bacterial species. PLoS One 10(5):e0126124

    PubMed Central  Article  PubMed  CAS  Google Scholar 

  • Hemberger S, Pedrolli DB, Stolz J, Vogl C, Lehmann M, Mack M (2011) RibM from Streptomyces davawensis is a riboflavin/roseoflavin transporter and may be useful for the optimization of riboflavin production strains. BMC Biotechnol 11

  • Henry CS, Zinner JF, Cohoon MP, Stevens RL (2009) iBsu1103: a new genome-scale metabolic model of Bacillus subtilis based on SEED annotations. Genome Biol 10(6):R69

    PubMed Central  Article  PubMed  CAS  Google Scholar 

  • Higashitsuji Y, Angerer A, Berghaus S, Hobl B, Mack M (2007) RibR, a possible regulator of the Bacillus subtilis riboflavin biosynthetic operon, in vivo interacts with the 5′-untranslated leader of rib mRNA. FEMS Microbiol Lett 274(1):48–54

    Article  PubMed  CAS  Google Scholar 

  • Hohmann HP, Mouncey NJ, Sauer U, Zamboni N (2011) Fermentation process. Patent EP 1 481 064 B1, 20 Feb 2003

  • Hümbelin M, Griesser V, Keller T, Schurter W, Haiker M, Hohmann HP, Ritz H, Richter G, Bacher A, van Loon A (1999) GTP cyclohydrolase II and 3,4-dihydroxy-2-butanone 4-phosphate synthase are rate-limiting enzymes in riboflavin synthesis of an industrial Bacillus subtilis strain used for riboflavin production. J Ind Microbiol Biotechnol 22(1):1–7

    Article  Google Scholar 

  • Jeong B-Y, Wittmann C, Kato T, Park EY (2015) Comparative metabolic flux analysis of an Ashbya gossypii wild type strain and a high riboflavin-producing mutant strain. J Biosci Bioeng 119(1):101–106

    Article  PubMed  CAS  Google Scholar 

  • Jiménez A, Santos MA, Pompejus M, Revuelta JL (2005) Metabolic engineering of the purine pathway for riboflavin production in Ashbya gossypii. Appl Microbiol Biotechnol 71(10):5743–5751

    Google Scholar 

  • Jiménez A, Santos MA, Revuelta JL (2008) Phosphoribosyl pyrophosphate synthetase activity affects growth and riboflavin production in Ashbya gossypii. BMC Biotechnol 8

  • Karrer P, Schöpp K, Benz F, Pfaehler K (1935) Synthesen von Flavinen III. Helv Chim Acta 18(1):69–79

    Article  CAS  Google Scholar 

  • Kato T, Park EY (2012) Riboflavin production by Ashbya gossypii. Biotechnol Lett 34(4):611–618

    Article  PubMed  CAS  Google Scholar 

  • Kind S, Kreye S, Wittmann C (2011) Metabolic engineering of cellular transport for overproduction of the platform chemical 1,5-diaminopentane in Corynebacterium glutamicum. Metab Eng 13(5):617–627

    Article  PubMed  CAS  Google Scholar 

  • Kirchner F, Mauch K, Schmid J (2014) Process for the production of riboflavin. Patent US 8,759,024 B2, 24 June 2014

  • Knorr B, Schlieker H, Hohmann H-P, Weuster-Botz D (2007) Scale-down and parallel operation of the riboflavin production process with Bacillus subtilis. Chem Eng J Bioch Eng 33(3):263–274

    Article  CAS  Google Scholar 

  • Kuhn R (1936) Lactoflavin (vitamin B2). Angew Chem 49(1):6–10

    Article  CAS  Google Scholar 

  • Kuhn R, György P, Wagner-Jauregg T (1933a) Über Lactoflavin, den Farbstoff der Molke. Ber Dtsch Chem Ges 66(7):1034–1038

    Article  Google Scholar 

  • Kuhn R, György P, Wagner-Jauregg T (1933b) Über Ovoflavin, den Farbstoff des Eiklars. Ber Dtsch Chem Ges 66(4):576–580

    Article  Google Scholar 

  • Ledesma-Amaro R, Kerkhoven EJ, Luis Revuelta J, Nielsen J (2014) Genome scale metabolic modeling of the riboflavin overproducer Ashbya gossypii. Biotechnol Bioeng 111(6):1191–1199

    Article  PubMed  CAS  Google Scholar 

  • Ledesma-Amaro R, Serrano-Amatriain C, Jimenez A, Revuelta JL (2015) Metabolic engineering of riboflavin production in Ashbya gossypii through pathway optimization. Microb Cell Fact 14(1):163

    PubMed Central  Article  PubMed  Google Scholar 

  • Lee K, Park Y, Han J, Park J, Choi H (2004) Microorganism for producing riboflavin and method for producing riboflavin using the same. Patent US2004/0110249A1, 10.06.2004

  • Lee KH, Park JH, Kim TY, Kim HU, Lee SY (2007) Systems metabolic engineering of Escherichia coli for L-threonine production. Mol Syst Biol 3

  • Lin ZQ, Xu ZB, Li YF, Wang ZW, Chen T, Zhao XM (2014) Metabolic engineering of Escherichia coli for the production of riboflavin. Microb Cell Fact 13

  • Mack M, van Loon A, Hohmann HP (1998) Regulation of riboflavin biosynthesis in Bacillus subtilis is affected by the activity of the flavokinase/flavin adenine dinucleotide synthetase encoded by ribC. J Bacteriol 180(4):950–955

    PubMed Central  PubMed  CAS  Google Scholar 

  • Malzahn RC, Phillips RF, Hanson AM (1959) Riboflavin process. Patent US 2,876,169, 03.03.1959

  • Man ZW, Rao ZM, Cheng YP, Yang TW, Zhang X, Xu MJ, Xu ZH (2014) Enhanced riboflavin production by recombinant Bacillus subtilis RF1 through the optimization of agitation speed. World J Microb Biot 30(2):661–667

    Article  CAS  Google Scholar 

  • Massey V (2000) The chemical and biological versatility of riboflavin. Biochem Soc Trans 28:283–296

    Article  PubMed  CAS  Google Scholar 

  • Mateos L, Jiménez A, Revuelta JL, Santos MA (2006) Purine biosynthesis, riboflavin production, and trophic-phase span are controlled by a Myb-related transcription factor in the fungus Ashbya gossypii. Appl Environ Microbiol 72(7):5052–5060

    PubMed Central  Article  PubMed  CAS  Google Scholar 

  • Matsui H, Sato K, Enei H, Hirose Y (1977) Mutation of an inosine-producing strain of Bacillus subtilis to dl-methionine sulfoxide resistance for guanosine production. Appl Environ Microbiol 34(4):337–341

    PubMed Central  PubMed  CAS  Google Scholar 

  • Matsui H, Sato K, Enei H, Hirose Y (1979) Production of guanosine by psicofuranine and decoyinine resistant mutants of Bacillus subtilis. Agric Biol Chem 43(8):1739–1744

    Article  CAS  Google Scholar 

  • Ming H, Pizarro AVL, Park EY (2003) Application of waste activated bleaching earth containing rapeseed oil on riboflavin production in the culture of Ashbya gossypii. Biotechnol Progr 19(2):410–417

    Article  CAS  Google Scholar 

  • Mironov AS, Gusarov I, Rafikov R, Lopez LE, Shatalin K, Kreneva RA, Perumov DA, Nudler E (2002) Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria. Cell 111(5):747–756

    Article  PubMed  CAS  Google Scholar 

  • Mitra S, Thawrani D, Banerjee P, Gachhui R, Mukherjee J (2012) Induced biofilm cultivation enhances riboflavin production by an intertidally derived Candida famata. Appl Biochem Biotechnol 166(8):1991–2006

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto Y, Sancar A (1998) Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals. PNAS 95(11):6097–6102

    PubMed Central  Article  PubMed  CAS  Google Scholar 

  • Monschau N, Sahm H, Stahmann KP (1998) Threonine aldolase overexpression plus threonine supplementation enhanced riboflavin production in Ashbya gossypii. Appl Environ Microbiol 64(11):4283–4290

    PubMed Central  PubMed  CAS  Google Scholar 

  • Northrop-Clewes CA, Thurnham DI (2012) The discovery and characterization of riboflavin. Ann Nutr Metab 61(3):224–230

    Article  PubMed  CAS  Google Scholar 

  • Oh Y-K, Palsson BO, Park SM, Schilling CH, Mahadevan R (2007) Genome-scale reconstruction of metabolic network in Bacillus subtilis based on high-throughput phenotyping and gene essentiality data. J Biol Chem 282(39):28791–28799

    Article  PubMed  CAS  Google Scholar 

  • O'Neil MJ (2006) Riboflavin. In: O'Neil MJ (ed) The Merck Index—Encyclopedia of chemicals, drugs & biologicals, vol 14. Whitehouse Station, New Jersey, p 1413

    Google Scholar 

  • Park EY, Ming H (2004) Oxidation of rapeseed oil in waste activated bleaching earth and its effect on riboflavin production in culture of Ashbya gossypii. J Biosci Bioeng 97(1):59–64

    Article  PubMed  CAS  Google Scholar 

  • Park EY, Kato A, Ming H (2004) Utilization of waste activated bleaching earth containing palm oil in riboflavin production by Ashbya gossypii. J Am Oil Chem Soc 81(1):57–62

    Article  CAS  Google Scholar 

  • Park EY, Ito Y, Nariyama M, Sugimoto T, Lies D, Kato T (2011) The improvement of riboflavin production in Ashbya gossypii via disparity mutagenesis and DNA microarray analysis. Appl Microbiol Biotechnol 91(5):1315–1326

    Article  PubMed  CAS  Google Scholar 

  • Pedrolli DB, Kühm C, Sévin DC, Vockenhuber MP, Sauer U, Suess B, Mack M (2015) A dual control mechanism synchronizes riboflavin and sulphur metabolism in Bacillus subtilis. PNAS

  • Perkins JB, Sloma A, Hermann T, Theriault K, Zachgo E, Erdenberger T, Hannett N, Chatterjee NP, Williams V, Rufo GA, Hatch R, Pero J (1999) Genetic engineering of Bacillus subtilis for the commercial production of riboflavin. J Ind Microbiol Biotechnol 22(1):8–18

    Article  CAS  Google Scholar 

  • Richter G, Fischer M, Krieger C, Eberhardt S, Luttgen H, Gerstenschlager I, Bacher A (1997) Biosynthesis of riboflavin: characterization of the bifunctional deaminase-reductase of Escherichia coli and Bacillus subtilis. J Bacteriol 179(6):2022–2028

    PubMed Central  PubMed  CAS  Google Scholar 

  • Rühl M, Zamboni N, Sauer U (2010) Dynamic flux responses in riboflavin overproducing Bacillus subtilis to increasing glucose limitation in fed-batch culture. Biotechnol Bioeng 105(4):795–804

    PubMed  Google Scholar 

  • Russo P, Capozzi V, Arena MP, Spadaccino G, Teresa Duenas M, Lopez P, Fiocco D, Spano G (2014) Riboflavin-overproducing strains of Lactobacillus fermentum for riboflavin-enriched bread. Appl Microbiol Biotechnol 98(8):3691–3700

    Article  PubMed  CAS  Google Scholar 

  • Sahm H, Antranikian G, Stahmann K-P, Takors R (2013) Riboflavin (vitamin B2). In: Sahm H, Antranikian G, Stahmann K-P, Takors R (eds) Industrielle Mikrobiologie. Springer-Verlag, Berlin-Heidelberg, pp 132–140

    Google Scholar 

  • Sauer U, Hatzimanikatis V, Bailey JE, Hochuli M, Szyperski T, Wüthrich K (1997) Metabolic fluxes in riboflavin-producing Bacillus subtilis. Nat Biotechnol 15(5):448–452

    Article  PubMed  CAS  Google Scholar 

  • Schlösser T, Wiesenburg A, Gaetgens C, Funke A, Viets U, Vijayalakshmi S, Nieland S, Stahmann KP (2007) Growth stress triggers riboflavin overproduction in Ashbya gossypii. Appl Microbiol Biotechnol 76(3):569–578

    Article  PubMed  CAS  Google Scholar 

  • Schlüpen C, Santos MA, Weber U, de Graaf A, Revuelta JL, Stahmann KP (2003) Disruption of the SHM2 gene, encoding one of two serine hydroxymethyltransferase isoenzymes, reduces the flux from glycine to serine in Ashbya gossypii. Biochem J 369:263–273

    PubMed Central  Article  PubMed  Google Scholar 

  • Schmidt G, Stahmann KP, Kaesler B, Sahm H (1996a) Correlation of isocitrate lyase activity and riboflavin formation in the riboflavin overproducer Ashbya gossypii. Microbiol 142:419–426

    Article  CAS  Google Scholar 

  • Schmidt G, Stahmann KP, Sahm H (1996b) Inhibition of purified isocitrate lyase identified itaconate and oxalate as potential antimetabolites for the riboflavin. Microbiol-Sgm 142:411–417

    Article  CAS  Google Scholar 

  • Shi SB, Chen T, Zhang ZG, Chen X, Zhao XM (2009a) Transcriptome analysis guided metabolic engineering of Bacillus subtilis for riboflavin production. Metab Eng 11(4–5):243–252

    Article  PubMed  CAS  Google Scholar 

  • Shi SB, Shen Z, Chen X, Chen T, Zhao XM (2009b) Increased production of riboflavin by metabolic engineering of the purine pathway in Bacillus subtilis. Biochem Eng J 46(1):28–33

    Article  CAS  Google Scholar 

  • Shi T, Wang YC, Wang ZW, Wang GL, Liu DY, Fu J, Chen T, Zhao XM (2014) Deregulation of purine pathway in Bacillus subtilis and its use in riboflavin biosynthesis. Microb Cell Fact 13

  • Silva R, Aguiar TQ, Domingues L (2015) Blockage of the pyrimidine biosynthetic pathway affects riboflavin production in Ashbya gossypii. J Biotechnol 193:37–40

    Article  PubMed  CAS  Google Scholar 

  • Stahmann KP, Böddecker T, Sahm H (1997) Regulation and properties of a fungal lipase showing interfacial inactivation by gas bubbles, or droplets of lipid or fatty acid. Eur J Biochem 244(1):220–225

    Article  PubMed  CAS  Google Scholar 

  • Stahmann KP, Revuelta JL, Seulberger H (2000) Three biotechnical processes using Ashbya gossypii, Candida famata, or Bacillus subtilis compete with chemical riboflavin production. Appl Microbiol Biotechnol 53(5):509–516

    Article  PubMed  CAS  Google Scholar 

  • Storhas W, Metz R (2006) Riboflavin—vitamin B2. In: Heinzle E, Biwer A, Cooney C (eds) Development of sustainable bioprocesses: modeling and assessment. John Wiley & Sons, Ltd., New Jersey, pp 167–177

    Google Scholar 

  • Sugimoto T, Kanamasa S, Kato T, Park EY (2009) Importance of malate synthase in the glyoxylate cycle of Ashbya gossypii for the efficient production of riboflavin. Appl Microbiol Biotechnol 83(3):529–539

    Article  PubMed  CAS  Google Scholar 

  • Sugimoto T, Morimoto A, Nariyama M, Kato T, Park EY (2010) Isolation of an oxalate-resistant Ashbya gossypii strain and its improved riboflavin production. J Ind Microbiol Biotechnol 37(1):57–64

    PubMed Central  Article  PubMed  CAS  Google Scholar 

  • Taniguchi H, Wendisch VF (2015) Exploring the role of sigma factor gene expression on production by Corynebacterium glutamicum: sigma factor H and FMN as example. Front Microbiol 6

  • Tanner JFW, Wickerham LJ, Van Lanen JM (1948) Biological process for the production of riboflavin. Patent US 2,445,128, 13.07.1948

  • Tännler S, Zamboni N, Kiraly C, Aymerich S, Sauer U (2008) Screening of Bacillus subtilis transposon mutants with altered riboflavin production. Metab Eng 10(5):216–226

    Article  PubMed  CAS  Google Scholar 

  • Wang GL, Bai L, Wang ZW, Shi T, Chen T, Zhao XM (2014) Enhancement of riboflavin production by deregulating gluconeogenesis in Bacillus subtilis. World J Microbiol Biotechnol 30(6):1893–1900

    Article  PubMed  CAS  Google Scholar 

  • Wolf R, Reiff F, Wittmann R, Butzke J (1983) Verfahren zur Herstellung von Riboflavin. Patent EP 0 020 959 B1, 29 June 1983

  • Yakimov AP, Seregina TA, Kholodnyak AA, Kreneva RA, Mironov AS, Perumov DA, Timkovskii AL (2014) Possible function of the ribT gene of Bacillus subtilis: theoretical prediction, cloning, and expression. Acta Nat 6(3):106–109

    CAS  Google Scholar 

  • Zamboni N, Mouncey N, Hohmann HP, Sauer U (2003) Reducing maintenance metabolism by metabolic engineering of respiration improves riboflavin production by Bacillus subtilis. Metab Eng 5(1):49–55

    Article  PubMed  CAS  Google Scholar 

  • Zhu Y, Chen X, Chen T, Shi S, Zhao X (2006) Over-expression of glucose dehydrogenase improves cell growth and riboflavin production in Bacillus subtilis. Biotechnol Lett 28(20):1667–1672

    Article  PubMed  CAS  Google Scholar 

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Affiliations

  1. Institute of Systems Biotechnology, Saarland University, Campus A1.5, 66123, Saarbrücken, Germany

    Susanne Katharina Schwechheimer, Judith Becker & Christoph Wittmann

  2. Laboratory of Biotechnology, Research Institute of Green Science and Technology, Shizuoka University, 836 Ohya Suruga-ku, Shizuoka, 422-8529, Japan

    Enoch Y. Park

  3. Departamento de Microbiología y Genética, Metabolic Engineering Group, Universidad de Salamanca, Laboratory 323, Edificio Departamental, Campus Miguel de Unamuno, 37007, Salamanca, Spain

    José Luis Revuelta

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  1. Susanne Katharina Schwechheimer
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  2. Enoch Y. Park
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  3. José Luis Revuelta
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  5. Christoph Wittmann
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Correspondence to Christoph Wittmann.

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Schwechheimer, S.K., Park, E.Y., Revuelta, J.L. et al. Biotechnology of riboflavin. Appl Microbiol Biotechnol 100, 2107–2119 (2016). https://doi.org/10.1007/s00253-015-7256-z

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Keywords

  • Riboflavin
  • Ashbya gossypii
  • Bacillus subtilis
  • Metabolic engineering
  • Vitamin B2