Skip to main content
Log in

Biotin in microbes, the genes involved in its biosynthesis, its biochemical role and perspectives for biotechnological production

  • Mini-Review
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract.

Biotin (vitamin H) is one of the most fascinating cofactors involved in central pathways in pro- and eukaryotic cell metabolism. Since its original discovery in 1901, research has led to the discovery of the complete biotin biosynthesis pathways in many different microbes and much work has been done on the highly intriguing and complex biochemistry of biotin biosynthesis. While humans and animals require several hundred micrograms of biotin per day, most microbes, plants and fungi appear to be able to synthesize the cofactor themselves. Biotin is added to many food, feed and cosmetic products, creating a world market of 10–30 t/year. However, the majority of the biotin sold is synthesized in a chemical process. Since the chemical synthesis is linked with a high environmental burden, much effort has been put into the development of biotin-overproducing microbes. A summary of biotin biosynthesis and its biological role is presented; and current strategies for the improvement of microbial biotin production using modern biotechnological techniques are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

References

  • Alexeev D et al (1994) Sequence and crystallization of Escherichia coli dethiobiotin synthetase, the penultimate enzyme of biotin biosynthesis. J Mol Biol 235:774–776

    Article  CAS  PubMed  Google Scholar 

  • Alexeev D, Alexeeva M, Baxter RL, Campopiano DJ, Webster SP, Sawyer L (1998) The crystal structure of 8-amino-7-oxononanoate synthase: a bacterial PLP-dependent, acyl-CoA-condensing enzyme. J Mol Biol 284:401–419

    Article  CAS  PubMed  Google Scholar 

  • Allison FE, Minor FW (1938) Coenzyme R requirements of rhizobia. Soil Sci 46:473–483

    CAS  Google Scholar 

  • Allison FE, Hoover SR, Burk D (1933) A respiratory coenzyme. Science 78

  • Baggiolini EG, Lee HL, Uskokovic MR (1983) Intermediates for the preparation of biotin. United States Patent 4,382,031

  • Baldet P, Ruffet ML (1996) Biotin synthesis in higher plants: isolation of a cDNA encoding Arabidopsis thaliana bioB-gene product equivalent by functional complementation of a biotin auxotroph mutant bioB105 of Escherichia coli K12. C R Acad Sci Ser D 319:99–106

    CAS  Google Scholar 

  • Baldet P, Alban C, Douce R (1997) Biotin synthesis in higher plants. Methods Enzymol 279:327–339

    CAS  PubMed  Google Scholar 

  • Bayer EA, Wilchek M (1990) Biotin-binding proteins: overview and prospects. Methods Enzymol 184:49–51

    CAS  PubMed  Google Scholar 

  • Beatrix B, Bendrat K, Rospert S, Buckel W (1990) The biotin-dependent sodium ion pump glutaconyl-CoA decarboxylase from Fusobacterium nucleatum (subsp. nucleatum). Comparison with the glutaconyl-CoA decarboxylases from gram-positive bacteria. Arch Microbiol 154:362–369

    CAS  PubMed  Google Scholar 

  • Beckett D, Matthews BW (1997) Escherichia coli repressor of biotin biosynthesis. Methods Enzymol 279:362–376

    CAS  PubMed  Google Scholar 

  • Bower S, Perkins JB, Pero J (1996a) Biotin biosynthesis in Bacillus subtilis. United States Patent 6,768,180

  • Bower S, Perkins JB, Yocum RR, Howitt CL, Rahaim P, Pero J (1996b) Cloning, sequencing, and characterization of the Bacillus subtilis biotin biosynthetic operon. J Bacteriol 178:4122–4130

    CAS  PubMed  Google Scholar 

  • Bower SG, Perkins JB, Yocum RR, Pero JG (2001) Biotin biosynthesis in Bacillus subtilis. United States Patent 6,303,377

  • Bratthauer GL (1999) The avidin-biotin complex (ABC) method and other avidin-biotin binding methods. Methods Mol Biol 115:203–214

    CAS  PubMed  Google Scholar 

  • Buckel W (2001) Sodium ion-translocating decarboxylases. Biochim Biophys Acta 1505:15–27

    Article  CAS  PubMed  Google Scholar 

  • Buckel W, Semmler R (1982) A biotin-dependent sodium pump: glutaconyl-CoA decarboxylase from Acidaminococcus fermentans. FEBS Lett 148:35–38

    Article  CAS  PubMed  Google Scholar 

  • Cleary PP, Campbell A (1972) Deletion and complementation analysis of biotin gene cluster of Escherichia coli. J Bacteriol 112:830–839

    CAS  PubMed  Google Scholar 

  • DeBaets S, Vandederink S, Vandamme EJ (2000) Vitamins and related biofactors, microbial production. Encycl Microbiol 4:837–853

    CAS  Google Scholar 

  • Del Campillo-Campbell A, Kayajanian G, Campbell A, Adhya S (1967) Biotin-requiring mutants of Escherichia coli K-12. J Bacteriol 94:2065–2066

    PubMed  Google Scholar 

  • Dimroth P (1985) Biotin-dependent decarboxylases as energy transducing systems. Ann NY Acad Sci 447:72–85

    CAS  PubMed  Google Scholar 

  • Dimroth P, Schink B (1998) Energy conservation in the decarboxylation of dicarboxylic acids by fermenting bacteria. Arch Microbiol 170:69–77

    Article  CAS  PubMed  Google Scholar 

  • Entcheva P, Liebl W, Johann A, Hartsch T, Streit WR (2001) Direct cloning from enrichment cultures, a reliable strategy for isolation of complete operons and genes from microbial consortia. Appl Environ Microbiol 67:89–99

    Article  CAS  PubMed  Google Scholar 

  • Entcheva P, Phillips DA, Streit WR (2002) Functional analysis of Sinorhizobium meliloti genes involved in biotin synthesis and transport. Appl Environ Microbiol 68:2843–2848

    Article  CAS  PubMed  Google Scholar 

  • Fall RR (1981) 3-Methylcrotonyl-CoA and geranyl-CoA carboxylases from Pseudomonas citronellolis. Methods Enzymol 71C:791–799

    Google Scholar 

  • Fleckenstein J, Kraemer B, Veits J (2001) Process for preparing biotin. United States Patent 6,291,681

  • Furuichi Y, Hoshino T, Kimura H, Kiyasu T, Nagahashi Y (2000) Biotin biosynthetic genes. United States Patent 6,117,669

  • Gloeckler R et al (1990) Cloning and characterization of the Bacillus sphaericus genes controlling the bioconversion of pimelate into dethiobiotin. Gene 87:63–70

    CAS  PubMed  Google Scholar 

  • Goldberg MW, Sternbach L (1949) United States Patent 2,489,237

  • Gompertz D, Draffan GH, Watts JL, Hull D (1971) Biotin-responsive beta-methylcrotonylglycinuria. Lancet 2:22–24

    CAS  PubMed  Google Scholar 

  • Green AJ et al (2001) Expression, purification and characterization of cytochrome P450 Biol: a novel P450 involved in biotin synthesis in Bacillus subtilis. J Biol Inorg Chem 6:523–533

    Article  CAS  PubMed  Google Scholar 

  • Guan X, Diez T, Prasad TK, Nikolau BJ, Wurtele ES (1999) Geranoyl-CoA carboxylase: a novel biotin-containing enzyme in plants. Arch Biochem Biophys 362:12–21

    Article  CAS  PubMed  Google Scholar 

  • Harris SA et al (1944) Biotin. II. Synthesis of biotin. J Am Chem Soc 66:1756–1757

    CAS  Google Scholar 

  • Hatakeyama K, Hohama K, Vertes AA, Kobayashi M, Kurusu Y, Yukawa H (1993a) Genomic organization of the biotin biosynthetic genes of coryneform bacteria: cloning and sequencing of the bioA–bioD genes from Brevibacterium flavum. DNA Seq 4:177–184

    CAS  PubMed  Google Scholar 

  • Hatakeyama K, Kohama K, Vertes AA, Kobayashi M, Kurusu Y, Yukawa H (1993b) Analysis of the biotin biosynthesis pathway in coryneform bacteria: cloning and sequencing of the bioB gene from Brevibacterium flavum. DNA Seq 4:87–93

    CAS  PubMed  Google Scholar 

  • Hector ML, Fall RR (1976) Multiple acyl-coenzyme A carboxylases in Pseudomonas citronellolis. Biochemistry 15:3465–3472

    CAS  PubMed  Google Scholar 

  • Heinz EB, Streit WR (2003) Sinorhizobium meliloti 1021 biotin-limitation alters transcription and translation. Appl Environ Microbiol (in press)

  • Heinz EB, Phillips DA, Streit WR (1999) BioS, a biotin-induced, stationary-phase, and possible LysR-type regulator in Sinorhizobium meliloti. Mol Plant-Microbe Interact 12:803–812

    CAS  Google Scholar 

  • Hoischen C, Kramer R (1990) Membrane alteration is necessary but not sufficient for effective glutamate secretion in Corynebacterium glutamicum. J Bacteriol 172:3409–3416

    CAS  PubMed  Google Scholar 

  • Hoshino T, Noro A, Tazoe M (1997) Process for the production of d-biotin. United States Patent 5,922,581

  • Huang W, Lindqvist Y, Schneider G, Gibson KJ, Flint D, Lorimer G (1994) Crystal structure of an ATP-dependent carboxylase, dethiobiotin synthetase, at 1.65 A resolution. Structure 2:407–414

    CAS  PubMed  Google Scholar 

  • Huang W et al (1995) Mechanism of an ATP-dependent carboxylase, dethiobiotin synthetase, based on crystallographic studies of complexes with substrates and a reaction intermediate. Biochemistry 34:10985–10995

    CAS  PubMed  Google Scholar 

  • Ifuku OHS, Kishimoto J, Koga N, Yanagi M, Fukushima S (1993) Sequencing analysis of mutation points in the biotin operon of biotin-overproducing Escherichia coli mutants. Biosci Biotechnol Biochem 57:760–765

    CAS  PubMed  Google Scholar 

  • Ifuku O, Koga N, Haze S, Kishimoto J, Arai T, Wachi Y (1995) Molecular analysis of growth inhibition caused by overexpression of the biotin operon in Escherichia coli. Biosci Biotechnol Biochem 59:184–189

    CAS  PubMed  Google Scholar 

  • Jetten MS, Sinskey AJ (1995) Recent advances in the physiology and genetics of amino acid-producing bacteria. Crit Rev Biotechnol 15:73–103

    CAS  PubMed  Google Scholar 

  • Kack H, Gibson KJ, Lindqvist Y, Schneider G (1998) Snapshot of a phosphorylated substrate intermediate by kinetic crystallography. Proc Natl Acad Sci USA 95:5495–5500

    Article  CAS  PubMed  Google Scholar 

  • Kack H, Sandmark J, Gibson K, Schneider G, Lindqvist Y (1999) Crystal structure of diaminopelargonic acid synthase: evolutionary relationships between pyridoxal-5'-phosphate-dependent enzymes. J Mol Biol 291:857–876

    Article  CAS  PubMed  Google Scholar 

  • Kanzaki N, Kawamoto T, Matsui J, Nakahama K, Ifuku O (2000) Microorganism resistant to threonine and production of biotin. United States Patent 6,020,173

  • Kanzaki N, Kawamoto T, Matsui J, Nakahama K, Ifuku O (2001) Microorganism resistant to threonine analogue and production of biotin. United States Patent 6,284,500

  • Karlsson S, Burman LG, Akerlund T (1999) Suppression of toxin production in Clostridium difficile VPI 10463 by amino acids. Microbiology 145:1683–1693

    CAS  PubMed  Google Scholar 

  • Kiyasu T, Asakura A, Nagahashi Y, Hoshino T (2000) Contribution of cysteine desulfurase (NifS protein) to the biotin synthase reaction of Escherichia coli. J Bacteriol 182:2879–2885

    CAS  PubMed  Google Scholar 

  • Kiyasu T, Nagahashi Y, Hoshino T (2001) Cloning and characterization of biotin biosynthetic genes of Kurthia sp. Gene 265:103–113

    Article  CAS  PubMed  Google Scholar 

  • Koga N, Kishimoto J, Haze S, Oi I (1996) Analysis of the bioH gene of Escherichia coli and its effect on biotin productivity. J Ferment Bioeng 81:482–487

    Article  CAS  Google Scholar 

  • Kögl F, Tönnis B (1936) Über das bios-problem. Darstellung von krystallisiertem Biotin aus Eigelb. Z Physiol Chem 242:43–73

    Google Scholar 

  • Lardy HA, Potter RL, Burris RH (1949) Metabolic functions of biotin I. The role of biotin in bicarbonate utilization by Lactobacillus arabinosis studied with 14C. J Biol Chem 179

  • Livnah O, Bayer E, Wilchek M, Sussman J (1993) Three-dimensional structures of avidin and the avidinbiotin complex. Proc Natl Acad Sci USA 90:5076–5080

    CAS  PubMed  Google Scholar 

  • Ludwig A, Stolz J, Sauer N (2000) Plant sucrose-H+ symporters mediate the transport of vitamin H. Plant J 24:503–509

    Article  CAS  PubMed  Google Scholar 

  • Lynen F, Knappe J, Lorch EJ, Ringelmann E, Lachance JP (1961) Zur biochemischen Funktion des Biotins. 2. Reinigung und Wirkungsweise der beta-methyl-crotonyl-caboxylase. Biochem Z 335:123

    CAS  Google Scholar 

  • Maegawa T et al (2002) Linkage between toxin production and purine biosynthesis in Clostridium difficile. J Med Microbiol 51:34–41

    CAS  PubMed  Google Scholar 

  • Marquet A, Bui BT, Florentin D (2001) Biosynthesis of biotin and lipoic acid. Vitam Horm 61:51–101

    CAS  PubMed  Google Scholar 

  • McMahon RJ (2002) Biotin in metabolism and molecular biology. Annu Rev Nutr 22:221–239

    Article  CAS  PubMed  Google Scholar 

  • Melville DB, Moyer AW, Hofmann K, Vigneaud V du (1942) The structure of biotin: the formation of thiophenevaleric acid from biotin. J Biol Chem 146:487–492

    CAS  Google Scholar 

  • Menendez C, Bauer Z, Huber H, Gad'on N, Stetter KO, Fuchs G (1999) Presence of acetyl coenzyme A (CoA) carboxylase and propionyl-CoA carboxylase in autotrophic Crenarchaeota and indication for operation of a 3-hydroxypropionate cycle in autotrophic carbon fixation. J Bacteriol 181:1088–1098

    CAS  PubMed  Google Scholar 

  • Moss J, Lane MD (1971) The biotin-dependent enzymes. Adv Enzymol Relat Areas Mol Biol 35:321–442

    CAS  PubMed  Google Scholar 

  • Ohsawa I et al (1989) Cloning of the biotin synthetase gene from Bacillus sphaericus and expression in Escherichia coli and Bacilli. Gene 80:39–48

    CAS  PubMed  Google Scholar 

  • Ollagnier-De-Choudens S, Mulliez E, Hewitson KS, Fontecave M (2002) Biotin synthase is a pyridoxal phosphate-dependent cysteine desulfurase. Biochemistry 41:9145–9152

    PubMed  Google Scholar 

  • O'Neil MJ, Smith A, Heckelman PE (eds) (2001) Merck index: an encyclopedia of chemicals, drugs, and biologicals. Merck, Whitehouse Station, N.J.

    Google Scholar 

  • O'Regan M, Gloeckler R, Bernard S, Ledoux C, Ohsawa I, Lemoine Y (1989) Nucleotide sequence of the bioH gene of Escherichia coli. Nucleic Acids Res 17:8004

    CAS  PubMed  Google Scholar 

  • Otsuka AJ et al (1988) The Escherichia coli biotin biosynthetic enzyme sequences predicted from the nucleotide sequence of the bio operon. J Biol Chem 263:19577–19585

    CAS  PubMed  Google Scholar 

  • Patton DA, Volrath S, Ward ER (1996) Complementation of an Arabidopsis thaliana biotin auxotroph with an Escherichia coli biotin biosynthetic gene. Mol Gen Genet 251:261–266

    Article  CAS  PubMed  Google Scholar 

  • Patton DA, Schetter AL, Franzmann LH, Nelson K, Ward ER, Meinke DW (1998) An embryo-defective mutant of Arabidopsis disrupted in the final step of biotin synthesis. Plant Physiol 116:935–946

    Article  CAS  PubMed  Google Scholar 

  • Phalip V, Kuhn I, Lemoine Y, Jeltsch JM (1999a) Characterization of the biotin biosynthesis pathway in Saccharomyces cerevisiae and evidence for a cluster containing BIO5, a novel gene involved in vitamer uptake. Gene 232:43–51

    Article  CAS  PubMed  Google Scholar 

  • Phalip V, Lemoine Y, Jeltsch JM (1999b) Cloning of Schizosaccharomyces pombe bio2 by heterologous complementation of a Saccharomyces cerevisiae mutant. Curr Microbiol 39:348–350

    Article  CAS  PubMed  Google Scholar 

  • Picciocchi A, Douce R, Alban C (2001) Biochemical characterization of the Arabidopsis biotin synthase reaction. The importance of mitochondria in biotin synthesis. Plant Physiol 127:1224–1233

    Article  CAS  PubMed  Google Scholar 

  • Rolfe B, Eisenberg MA (1968) Genetic and biochemical analysis of the biotin loci of Escherichia coli K-12. J Bacteriol 96:515–524

    CAS  PubMed  Google Scholar 

  • Romero-Navarro G et al (1999) Biotin regulation of pancreatic glucokinase and insulin in primary cultured rat islets and in biotin-deficient rats. Endocrinology 140:4595–4600

    CAS  PubMed  Google Scholar 

  • Sakurai N, Imai Y, Masuda M, Komatsubara S, Tosa T (1993) Construction of a biotin-overproducing strain of Serratia marcescens. Appl Environ Microbiol 59:2857–2863

    CAS  Google Scholar 

  • Sakurai N, Imai Y, Masuda M, Komatsubara S, Tosa T (1994) Improvement of a d-biotin-hyperproducing recombinant strain of Serratia marcescens. J Biotechnol 36:63–73

    Google Scholar 

  • Sanyal I, Cohen G, Flint DH (1994) Biotin synthase: purification, characterization as a [2Fe–2S]cluster protein, and in vitro activity of the Escherichia coli bioB gene product. Biochemistry 33:3625–3631

    CAS  PubMed  Google Scholar 

  • Schmidt A et al (2001) Three-dimensional structure of 2-amino-3-ketobutyrate CoA ligase from Escherichia coli complexed with a PLP-substrate intermediate: inferred reaction mechanism. Biochemistry 40:5151–5160

    Article  CAS  PubMed  Google Scholar 

  • Serebriiskii IG, Vassin VM, Tsygankov YD (1996) Two new members of the bioB superfamily: cloning, sequencing and expression of bioB genes of Methylobacillus flagellatum and Corynebacterium glutamicum. Gene 175:15–22

    Article  CAS  PubMed  Google Scholar 

  • Shaw N et al (1999) Biotin production under limiting growth conditions by Agrobacterium/Rhizobium HK4 transformed with a modified Escherichia coli bio operon. J Ind Microbiol Biotechnol 22:590–599

    Article  CAS  PubMed  Google Scholar 

  • Stok JE, De Voss J (2000) Expression, purification, and characterization of BioI: a carbon-carbon bond cleaving cytochrome P450 involved in biotin biosynthesis in Bacillus subtilis. Arch Biochem Biophys 384:351–360

    Article  CAS  PubMed  Google Scholar 

  • Streaker ED, Beckett D (1998) A map of the biotin repressor-biotin operator interface: binding of a winged helix-turn-helix protein dimer to a forty base-pair site. J Mol Biol 278:787–800

    Article  CAS  PubMed  Google Scholar 

  • Streit WR, Phillips DA (1996) Recombinant Rhizobium meliloti strains with extra biotin synthesis capability. Appl Environ Microbiol 62:3333–3338

    CAS  PubMed  Google Scholar 

  • Streit WR, Phillips DA (1997) A biotin-regulated locus, bioS, in a possible survival operon of Rhizobium meliloti. Mol Plant-Microbe Interact 10:933–937

    CAS  Google Scholar 

  • Streit WR, Joseph CM, Phillips DA (1996) Biotin and other water-soluble vitamins are key growth factors for alfalfa root colonization by Rhizobium meliloti 1021. Mol Plant-Microbe Interact 9:330–338

    CAS  Google Scholar 

  • Sullivan JT, Brown SD, Yocum RR, Ronson CW (2001) The bio operon on the acquired symbiosis island of Mesorhizobium sp. strain R7A includes a novel gene involved in pimeloyl-CoA synthesis. Microbiology 147:1315–1322

    CAS  PubMed  Google Scholar 

  • Tomczyk NH, Nettleship JE, Baxter RL, Crichton HJ, Webster SP, Campopiano DJ (2002) Purification and characterisation of the BioH protein from the biotin biosynthetic pathway. FEBS Lett 513:299–304

    Article  CAS  PubMed  Google Scholar 

  • Ugulava NB, Gibney BR, Jarrett JT (2000) Iron–sulfur cluster interconversions in biotin synthase: dissociation and reassociation of iron during conversion of [2Fe–2S] to [4Fe–4S] clusters. Biochemistry 39:5206–5214

    CAS  PubMed  Google Scholar 

  • Ugulava NB, Gibney BR, Jarrett JT (2001) Biotin synthase contains two distinct iron–sulfur cluster binding sites: chemical and spectroelectrochemical analysis of iron–sulfur cluster interconversions. Biochemistry 40:8343–8351

    CAS  PubMed  Google Scholar 

  • Vigneaud V du, Melville DB, Gyorgy P (1941a) Isolation of biotin (vitamin H) from liver. J Biol Chem 140:643–651

    Google Scholar 

  • Vigneaud V du, Melville DB, Rachele J (1941b) The preparation of free crystalline biotin. J Biol Chem 140:763–766

    Google Scholar 

  • Wakil SJ, Titchener EB, Gibson DM (1958) Evidence for the participation of biotin in the enzymic synthesis of fatty acids. Biochem Biophys Acta 29:225–226

    CAS  Google Scholar 

  • Weaver LM, Yu F, Wurtele ES, Nikolau BJ (1996) Characterization of the cDNA and gene coding for the biotin synthase of Arabidopsis thaliana. Plant Physiol 110:1021–1028

    Article  CAS  PubMed  Google Scholar 

  • Webster SP et al (2000) Mechanism of 8-amino-7-oxononanoate synthase: spectroscopic, kinetic, and crystallographic studies. Biochemistry 39:516–528

    Article  CAS  PubMed  Google Scholar 

  • Wessman GE, Werkman CH (1950) Biotin in the assimilation of heavy carbon in oxalacetate. Arch Biochem Biophys 26

  • Whitney PA, Cooper TG (1972) Urea carboxylase and allophanate hydrolase. Two components of adenosine triphosphate:urea amido-lyase in Saccharomyces cerevisiae. J Biol Chem 247:1349–1353

    CAS  PubMed  Google Scholar 

  • Wildiers E (1901) Nouvelle substance indispensable au developpement de la levure. La Cellule 18:313–316

    Google Scholar 

  • Wilson KP, Shewchuk LM, Brennan RG, Otsuka AJ, Matthews BW (1992) Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. Proc Natl Acad Sci USA 89:9257–9261

    CAS  PubMed  Google Scholar 

  • Wolf B, Grier RE, Parker WD Jr, Goodman SI, Allen RJ (1983) Deficient biotinidase activity in late-onset multiple carboxylase deficiency. N Engl J Med 308:161

    CAS  Google Scholar 

  • Wolf B, Grier RE, Secor McVoy JR, Heard GS (1985) Biotinidase deficiency: a novel vitamin recycling defect. J Inherit Metab Dis 8 [Suppl 1]:53–58

  • Wu SC, Wong SL (2002) Engineering of a Bacillus subtilis strain with adjustable levels of intracellular biotin for secretory production of functional streptavidin. Appl Environ Microbiol 68:1102–1108

    Article  CAS  PubMed  Google Scholar 

  • Yamada H, Osakai M, Tani Y, Izumi Y (1983) Biotin overproduction by biotin analog-resistant mutants of Bacillus sphaericus. Agric Biol Chem 47:1011–1016

    CAS  Google Scholar 

  • Yamakawa K, Karasawa T, Ikoma S, Nakamura S (1996) Enhancement of Clostridium difficile toxin production in biotin-limited conditions. J Med Microbiol 44:111–114

    CAS  PubMed  Google Scholar 

  • Yamakawa K, Karasawa T, Ohta T, Hayashi H, Nakamura S (1998) Inhibition of enhanced toxin production by Clostridium difficile in biotin-limited conditions. J Med Microbiol 47:767–771

    CAS  PubMed  Google Scholar 

  • Zhang S, Sanyal I, Bulboaca GH, Rich A, Flint DH (1994) The gene for biotin synthase from Saccharomyces cerevisiae: cloning, sequencing, and complementation of Escherichia coli strains lacking biotin synthase. Arch Biochem Biophys 309:29–35

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements.

The Deutsche Bundesstiftung Umwelt and the Fonds der chemischen Industrie supported this work. P.E. and W.R.S. thank W. Liebl for helpful discussions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to W. R. Streit.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Streit, W.R., Entcheva, P. Biotin in microbes, the genes involved in its biosynthesis, its biochemical role and perspectives for biotechnological production. Appl Microbiol Biotechnol 61, 21–31 (2003). https://doi.org/10.1007/s00253-002-1186-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-002-1186-2

Keywords

Navigation