Skip to main content

Advertisement

Log in

Firefly luciferase: an adenylate-forming enzyme for multicatalytic functions

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Firefly luciferase is a member of the acyl-adenylate/thioester-forming superfamily of enzymes and catalyzes the oxidation of firefly luciferin with molecular oxygen to emit light. Knowledge of the luminescence mechanism catalyzed by firefly luciferase has been gathered, leading to the discovery of a novel catalytic function of luciferase. Recently, we demonstrated that firefly luciferase has a catalytic function of fatty acyl-CoA synthesis from fatty acids in the presence of ATP, Mg2+ and coenzyme A. Based on identification of fatty acyl-CoA genes in firefly, Drosophila, and non-luminous click beetles, we then proposed that the evolutionary origin of firefly luciferase is a fatty acyl-CoA synthetase in insects. Further, we succeeded in converting the fatty acyl-CoA synthetase of non-luminous insects into functional luciferase showing luminescence activity by site-directed mutagenesis.

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

Access this article

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15

Similar content being viewed by others

References

  1. Harvey EN (1952) Bioluminescence. Academic, New York

    Google Scholar 

  2. Haneda Y, Johnson FH (eds) (1966) Bioluminescence in progress. Princeton University Press, New Jersey

    Google Scholar 

  3. Herring PJ (ed) (1978) Bioluminescence in action. Academic, New York

    Google Scholar 

  4. Campbell AK (1988) Chemiluminescence: principle and applications in biology and medicine. VCH, New York

    Google Scholar 

  5. Shimomura O (2006) Bioluminescence: chemical principles and methods. World Scientific, Singapore

    Google Scholar 

  6. Shimomura O (1985) Bioluminescence in the sea: photoprotein systems. Soc Exp Biol Symp 39:351–372

    CAS  Google Scholar 

  7. Hastings JW, Morin JG (1991) Bioluminescence. In: Prosser CL (ed) Neural and integrative animal physiology. Wiley, New York, pp 131–170

  8. Meighen EA, Dunlap PV (1993) Physiological, biochemical and genetic control of bacterial bioluminescence. Adv Microbial Physiol 34:1–67

    CAS  Google Scholar 

  9. Wilson T, Hastings JW (1998) Bioluminescence. Annu Rev Cell Dev Biol 14:197–230

    CAS  PubMed  Google Scholar 

  10. Bronstein I, Fortin J, Stanley PE, Stewart GSAB, Kricka LJ (1994) Chemiluminescent and bioluminescent reporter gene assays. Anal Biochem 219:169–181

    CAS  PubMed  Google Scholar 

  11. Greer LF III, Szalay AA (2002) Imaging of light emission from the expression of luciferases in living cells and organisms: a review. Luminescence 17:43–73

    CAS  PubMed  Google Scholar 

  12. Lloyd JE (1983) Bioluminescence and communication in insects. Annu Rev Entomol 28:131–160

    Google Scholar 

  13. Wood KV (1995) The chemical mechanism and evolutionary development of beetle bioluminescence. Photochem Photobiol 62:662–673

    CAS  Google Scholar 

  14. Viviani VR (2002) The origin, diversity, and structure function relationships of insect luciferases. Cell Mol Life Sci 59:1833–1850

    CAS  PubMed  Google Scholar 

  15. Nakamura M, Niwa K, Maki S, Hirano T, Ohmiya Y, Niwa H (2006) Conversion of a new firefly bioluminescence system using l-luciferin as substrate. Tetrahedron Lett 47:1197–1200

    CAS  Google Scholar 

  16. McElroy WD, DeLuca M, Travis J (1967) Molecular uniformity in biological catalyses. Science 157:150–160

    CAS  PubMed  Google Scholar 

  17. Oba Y, Ojika M, Inouye S (2003) Firefly luciferase is a bifunctional enzyme: ATP-dependent monooxygenase and a long chain fatty acyl-CoA synthetase. FEBS Lett 540:251–254

    CAS  PubMed  Google Scholar 

  18. Bitler B, McElroy WD (1957) The preparation and properties of crystalline firefly luciferin. Arch Biochem Biophys 72:358–368

    CAS  PubMed  Google Scholar 

  19. Kishi Y, Matsuura S, Inoue S, Shimomura O, Goto T (1968) Luciferin and luciopterin isolated from the Japanese firefly, Luciola cruciata. Tetrahedron Lett 9:2847–2850

    Google Scholar 

  20. White EH, McCapra F, Field GF, McElroy WD (1961) The structure and synthesis of firefly luciferin. J Am Chem Soc 83:2402–2403

    CAS  Google Scholar 

  21. White EH, McCapra F, Field GF (1963) The structure and synthesis of firefly luciferin. J Am Chem Soc 85:337–343

    CAS  Google Scholar 

  22. Blank GE, Pletcher J, Sax M (1971) The molecular structure of firefly d-(−)-luciferin: a single crystal analysis. Biochem Biophys Res Commun 42:583–588

    CAS  PubMed  Google Scholar 

  23. Branchini BR, Magyar RA, Murtiashaw MH, Porieer NC (2001) The role of active site residue arginine 218 in firefly luciferase. Biochemistry 40:2410–2418

    CAS  PubMed  Google Scholar 

  24. Oba Y, Shintani T, Nakamura T, Ojika M, Inouye S (2008) Determination of the luciferin contents in luminous and non-luminous beetles. Biochem Biosci Biotechnol 272:384–1387

    Google Scholar 

  25. Seliger HH, McElroy WD, White EH, Field GF (1961) Stereospecificity and firefly bioluminescence, a comparison of natural and synthetic luciferins. Proc Natl Acad Sci USA 47:1129–1961

    CAS  PubMed  Google Scholar 

  26. Lembert N (1996) Firefly luciferase can use l-luciferin to produce light. Biochem J 317:273–277

    CAS  PubMed  Google Scholar 

  27. Niwa K, Nakamura M, Ohmiya Y (2006) Stereoisomeric bio-inversion key to biosynthesis of firefly d-luciferin. FEBS Lett 580:5283–5287

    CAS  PubMed  Google Scholar 

  28. Rhodes WC, McElroy WD (1958) The synthesis and function of luciferyl-adenylate and oxyluciferyl-adenylate. J Biol Chem 233:1528–1537

    CAS  PubMed  Google Scholar 

  29. Seliger HH, McElroy WD (1962) Chemiluminescence of firefly luciferin without enzyme. Science 138:683–685

    CAS  PubMed  Google Scholar 

  30. Suzuki N, Sato M, Nishikawa K, Goto T (1969) Synthesis and spectral properties of 2-(6′-hydroxybenzothiazol-2′-yl)-4-hydroxytiazole, a possible emitting species in the firefly bioluminescence. Tetrahedron Lett 53:4683–4684

    Google Scholar 

  31. Suzuki N, Goto T (1971) Firefly bioluminescence II. Identification of 2-(6′-hydroxybenzothiazol-2′-yl)-4-hydroxythiazole as a product in the bioluminescence of firefly lanterns and a product in the chemiluminescence of firefly luciferin in DMSO. Tetrahedron Lett 22:2021–2024

    Google Scholar 

  32. Suzuki N, Goto T (1972) Synthesis of 4-thiazolone derivatives related to firefly luciferin. Agric Biol Chem 36:2213–2221

    CAS  Google Scholar 

  33. Hopkins TA, Seliger HH, White EH, Cass MW (1969) The chemiluminescence of firefly luciferin. A model for the bioluminescent reaction and identification if the product excited state. J Am Chem Soc 89:7148–7150

    Google Scholar 

  34. Esteves da Silva JCG, Magalhaes JMCS, Fontes T (2001) Identification of enzyme produced firefly oxyluciferin by reverse phase HPLC. Tetrahedron Lett 42:8173–8176

    CAS  Google Scholar 

  35. Ribeiro C, Esteves da Silva JC (2008) Kinetics of inhibition of firefly luciferase by oxyluciferin and dehydroluciferyl-adenylate. Photochem Photobiol 7:1085–1090

    CAS  Google Scholar 

  36. Branchini BR, Murtiashaw MH, Magyer RA, Anderson SM (2000) The role of lysine 529, a conserved residue of the acyl-adenylate-forming enzyme superfamily, in firefly luciferase. Biochemistry 39:5433–5440

    CAS  PubMed  Google Scholar 

  37. Imai K, Goto T (1988) Improved synthesis of firefly d-luciferyl–d-adenylate—A key intermediate of firefly bioluminescence. Agric Biol Chem 52:2803–2809

    CAS  Google Scholar 

  38. White EH, Steinmetz MG, Miano JD, Wildes PD, Morland R (1980) Chemi- and bioluminescence of firefly luciferin. J Am Chem Soc 102:3199–3208

    CAS  Google Scholar 

  39. Shimomura O, Goto T, Johnson FH (1977) Source of oxygen in the CO2 produced in the bioluminescent oxidation of firefly luciferin. Proc Natl Acad Sci USA 74:2799–2802

    CAS  PubMed  Google Scholar 

  40. McCapra F (1977) Alternative mechanism of dioxetanone decomposition. J Chem Soc Chem Commun (1977) 946–948

  41. Koo J-Y, Schmidt SP, Schuster GB (1978) Bioluminescence of the firefly: key steps in the formation of the electronically excited state for model systems. Proc Natl Acad Sci USA 84:131–135

    Google Scholar 

  42. Seliger HH, McElroy WD (1960) Spectral emission and quantum yield of firefly bioluminescence. Arch Biochem Biophys 88:136–141

    CAS  PubMed  Google Scholar 

  43. White EH, Roswell DF (1991) Analogs and derivatives of firefly oxyluciferin, the light emitter in firefly bioluminescence. Photochem Photobiol 53:131–136

    CAS  PubMed  Google Scholar 

  44. Kajiyama N, Nakano E (1991) Isolation and characterization of mutants of firefly luciferase which produced different color of light. Protein Eng 4:691–693

    CAS  PubMed  Google Scholar 

  45. Branchini BR, Murtiashaw MH, Magyar RA, Protier NC, Ruggiero MC, Stroh JG (2002) Yellow-green and red firefly bioluminescence from 5,5′-dimethoxyluciferin. J Am Chem Soc 124:2112–2113

    CAS  PubMed  Google Scholar 

  46. McCapra F, Gilfoyle DJ, Young DW, Church NJ, Spencer P (1994) The chemical origin of color differences in beetle bioluminescence. In: Campbell AK, Kricka LJ, Stanley PE (eds) Bioluminescence and chemiluminescence. Fundamentals and applied aspects. Wiley, Chichester, UK, pp 387–391

    Google Scholar 

  47. McCapra F (1997) Mechanism in chemiluminescence and bioluminescence—unfinished business. In: Hastings JW, Kricka LJ, Stanley PE (eds) Bioluminescence and chemiluminescence molecular reporting with photons. Wiley, Chichester, UK, pp 7–15

    Google Scholar 

  48. Branchini RB, Southworth TL, Murtiashaw MH, Magyar RA, Gonzalez SA, Ruggiero MC, Stroh JG (2004) An alternative mechanism of bioluminescence color determination in firefly luciferase. Biochemistry 43:7255–7262

    CAS  PubMed  Google Scholar 

  49. Orlova G, Goddard JD, Brovko LY (2003) The theoretical study of the amazing firefly bioluminescence: the formation and structures of the light emitters. J Am Chem Soc 125:6962–6971

    CAS  PubMed  Google Scholar 

  50. Yang T, Goddard JD (2007) Prediction of the geometries and florescence emission energies of oxyluciferins. J Phys Chem 111:4489–4497

    CAS  Google Scholar 

  51. Nakatani N, Hasegawa J, Nakatuji H (2007) Red light in chemiluminescence and yellow-green light in bioluminescence: color-turning mechanism of firefly, Photinus pyralis, studied by the symmetry-adapted cluster-conjugation interaction method. J Am Chem Soc 129:8756–8765

    CAS  PubMed  Google Scholar 

  52. Hirano T, Hasumi Y, Ohtsuka K, Maki S, Niwa H, Yamaji M, Hashizume D (2009) Spectroscopic studies of the light-color modulation mechanism of firefly (beetle) bioluminescence. J Am Chem Soc 131:2385–2396

    CAS  PubMed  Google Scholar 

  53. DeLuca M, McElroy WD (1978) Purification and properties of firefly luciferase. Methods Enzymol 57:3–15

    CAS  Google Scholar 

  54. DeLuca M, Wannlund J, McElroy WD (1979) Factors affecting the kinetics of light emission from crude and purified firefly luciferase. Anal Biochem 95:194–198

    CAS  PubMed  Google Scholar 

  55. Webster JJ, Chang JC, Manley ER, Spivey HO, Leach FR (1980) Buffer effects on ATP analysis by firefly luciferase. Anal Biochem 106:7–11

    CAS  PubMed  Google Scholar 

  56. Simpson WJ, Hammond JRM (1991) The effect of detergents on firefly luciferase reaction. J Biolumi Chemilumi 6:97–106

    CAS  Google Scholar 

  57. Ford SR, Chenault KH, Bunton LS, Hampton GJ, McCarthy J, Hall MS, Pangburn SJ, Buck LM, Leach FR (1996) Use of firefly luciferase for ATP measurement: other nucleotides enhance turnover. J Biolumi Chemilumi 11:149–167

    CAS  Google Scholar 

  58. Airth RL, Rhodes WC, McElroy WD (1958) The function of coenzyme A in luminescence. Biochim Biophys Acta 27:519–532

    CAS  PubMed  Google Scholar 

  59. Roda A, Guardigli M, Michelini E, Mirasoli M (2009) Bioluminescence in analytical chemistry and in vivo imaging. Trends Anal Chem 28:307–322

    CAS  Google Scholar 

  60. Seliger HH, McElroy WD (1959) Quantum yield in the oxidation of firefly luciferin. Biochem Biophys Res Commun 1:21–24

    CAS  Google Scholar 

  61. Ando Y, Niwa K, Yamada N, Enomoto T, Irie T, Kubota H, Ohmiya Y, Akiyama H (2008) Firefly bioluminescence quantum yield and color change by pH-sensitive green emission. Nat Photon 2:44–46

    CAS  Google Scholar 

  62. Fraga H, Esteves da Silva JCG, Fontes R (2006) Identification of luciferyl adenylate and luciferyl coenzyme A synthesized by firefly luciferase. Chem Bio Chem 5:110–115

    Google Scholar 

  63. Okada K, Iio H, Kubota I, Goto T (1974) Firefly bioluminescence. III. Conversion of oxyluciferin to luciferin in firefly. Tetrahedron Lett 32:2771–2774

    Google Scholar 

  64. Okada K, Iio H, Goto T (1976) Biosynthesis of firefly luciferin. Probable formation of benzothiazole from p-benzoquinone and cysteine. J Chem Soc Chem Comm (1976) 32

  65. McCapra F, Razavi Z (1975) A model for firefly luciferin biosynthesis. J Chem Soc Chem Comm (1975) 42–43

  66. McCapra F, Razavi Z (1976) Biosynthesis of luciferin in Pyroporus pellucens. J Chem Soc Chem Commun (1976) 153–154

  67. Gomi K, Kajiyama N (2001) Oxyluciferin, a luminescence product of firefly luciferase, is enzymatically regenerated into luciferin. J Biol Chem 276:36508–36513

    CAS  PubMed  Google Scholar 

  68. Gomi K, Hiorkawa K, Kajiyama N (2002) Molecular cloning and expression of the cDNAs encoding luciferin-regenerating enzyme from Luciola cruciata and Luciola lateralis. Gene 294:157–166

    CAS  PubMed  Google Scholar 

  69. Day JC, Tisi L, Bailey MJ (2004) Evolution of beetle bioluminescence: the origin of beetle luciferin. Luminescence 19:8–20

    CAS  PubMed  Google Scholar 

  70. Marques SM, Estreves da Silva JCG (2009) Firefly bioluminescence: a mechanistic approach of luciferase catalyzed reactions. IUBMB Life 61:6–17

    CAS  PubMed  Google Scholar 

  71. Oba Y, Kato S, Ojika M, Inouye S (2002) Biosynthesis of luciferin in the sea firefly, Cypridina hilgendorfii: l-tryptophan is a component in Cypridina luciferin. Tetrahedron Lett 43:2389–2392

    CAS  Google Scholar 

  72. Kato S, Oba Y, Ojika M, Inouye S (2004) Identification of the biosynthetic units of Cypridina luciferin in Cypridina (Vargula) hilgendorfii by LC/ESI-TOF-MS. Tetrahedron 60:11427–11434

    CAS  Google Scholar 

  73. White EH, Wörther H, Field GF, McElroy WD (1965) Analogs of firefly luciferin. J Org Chem 30:2344–2348

    CAS  Google Scholar 

  74. White EH, Wörther H, Seliger HH, McElroy WD (1966) Amino analogs of firefly luciferin and biological activity thereof. J Am Chem Soc 88:2015–2019

    CAS  Google Scholar 

  75. White EH, Wörther H (1966) Analogs of firefly luciferin. III. J Org Chem 31:1484–1488

    CAS  PubMed  Google Scholar 

  76. White EH, Rapaport E, Hopkins TA, Seliger HH (1969) Chemi- and bioluminescence of firefly luciferin. J Am Chem Soc 91:2178–2180

    CAS  PubMed  Google Scholar 

  77. Seto S, Ogura K, Nishiyama Y (1963) A convenient synthetic method of 2-carbamoyl-6-methoxybenzothiazole, one of intermediates for the synthesis of firefly luciferin. Bull Chem Soc Jpn 36:331–333

    CAS  Google Scholar 

  78. France C, Blanchot B, Champiar D, Couble P, Declercq G, Millet J-L (1990) Synthesis and characterization of a new substrate of Photinus pyralis luciferase: 4-methyl-d-luciferin. J Clin Chem Clin Biochem 28:471–474

    Google Scholar 

  79. Woodroofe CC, Shultz JW, Wood MG, Osterman J, Cali JJ, Daily WJ, Meisenheimer PL, Klaubert DH (2008) N-Alkylated 6′-aminoluciferins are bioluminescent substrates for Ultra-Glo and QuantiLum luciferase: new potential scaffolds for bioluminescent assays. Biochemistry 47:10383–10393

    CAS  PubMed  Google Scholar 

  80. Branchini BR, Hayward MM, Bamford S, Brennan PM, Lajiness EJ (1989) Naphtyl- and quinolyllucifferin: green and red light emitting firefly luciferin analogues. Photochem Photobiol 49:689–695

    CAS  PubMed  Google Scholar 

  81. Miska W, Geiger R (1987) Synthesis and characterization of luciferin derivatives for use in bioluminescence enhanced enzyme immunoassays. J Clin Chem Clin Biochem 25:23–30

    CAS  PubMed  Google Scholar 

  82. Geiger R, Miska W (1987) Bioluminescence enhanced enzyme immunoassay. J Clin Chem Clin Biochem 25:31–38

    CAS  PubMed  Google Scholar 

  83. Miska W, Geiger R (1989) Luciferin derivatives in bioluminescence-enhanced enzyme immunoassays. J Biolumi Chemilumi 4:119–128

    CAS  Google Scholar 

  84. Hauber R, Geiger R (1988) A sensitive, bioluminescent-enhanced detection method for DNA-dot-hybridization. Nucl Acids Res 16:1213

    CAS  PubMed  Google Scholar 

  85. Huber R, Geiger R (1987) A new, very sensitive, bioluminescence-enhanced detection system for protein blotting. Ultrasensitive detection systems for protein blotting and DNA hybridization, I. J Clin Chem Clin Biochem 25:511–514

    Google Scholar 

  86. Amess R, Baggett N, Darby PR, Goode AR, Vickers EE (1990) Synthesis of luciferin glycoside as substrate for novel ultrasensitive enzyme assays. Carbohydrate Res 205:225–233

    CAS  Google Scholar 

  87. Monsees T, Miska W, Geiger R (1994) Synthesis and characterization of a bioluminogenic substrate for α-chymotrypsin. Anal Biochem 221:329–334

    CAS  PubMed  Google Scholar 

  88. Sudhaharan T, Reddy AR (1999) A bifunctional luminogenic substrate for two luminescent enzymes: firefly luciferase and horseradish peroxidase. Anal Biochem 271:159–167

    CAS  PubMed  Google Scholar 

  89. Zhou W, Valley MP, Shultz J, Hawkins EM, Bernad L, Good T, Good D, Riss TL, Klaubert DH, Wood KV (2006) New bioluminogenic substrates for monoamine oxidase assays. J Am Chem Soc 128:3122–3123

    CAS  PubMed  Google Scholar 

  90. Valley MP, Zhou W, Hawkins EM, Shultz J, Cali JJ, Worzella T, Bernad L, Good T, Good D, Riss TL, Klaubert DH, Wood KV (2006) A bioluminescent assay for monoamine oxidase activity. Anal Biochem 359:236–246

    Google Scholar 

  91. Craig FF, Simmonds AC, Watmore D, McCapra F, White MRH (1991) Membrane-permeable luciferin esters for assay of firefly luciferase in live intact cells. Biochem J 276:637–641

    CAS  PubMed  Google Scholar 

  92. Yong J, Thompson DB (1993) An easily synthesized, photolyzable luciferase substrate for in vivo luciferase activity measurement. Biotechniques 15:848–850

    Google Scholar 

  93. Shinde R, Perkins J, Contag CH (2006) Luciferin derivatives for enhanced in vitro and in vivo bioluminescence assays. Biochemistry 45:11103–11112

    CAS  PubMed  Google Scholar 

  94. Jones LR, Goun EA, Shinde R, Rothbard JB, Contag CH, Wender PA (2006) Releasable luciferin-transporter conjugates: tools for the real-time analysis of cellular uptake and release. J Am Chem Soc 128:6526–6527

    CAS  PubMed  Google Scholar 

  95. Wender PA, Goun EA, Jones LR, Pillow TH, Rothbard JB, Shinde R, Contag CH (2007) Real-time analysis of uptake and bioactivatable cleavage of luciferin-transporter conjugates in transgenic reporter mice. Proc Natl Acad Sci USA 104:10340–10345

    CAS  PubMed  Google Scholar 

  96. Chandran SS, Williams SA, Denmeade SR (2008) Extended-release PEG-luciferin allows for long-term imaging of firefly luciferase activity in vivo. Luminescence 24:35–38

    Google Scholar 

  97. Gates BJ, DeLuca M (1975) The production of oxyluciferin during the firefly luciferase light reaction. Arch Biochem Biophys 169:616–621

    CAS  PubMed  Google Scholar 

  98. McElroy WD, Hastings JW, Coulombre J, Sonnenfeld V (1953) The mechanism of action of pyrophosphate in firefly luminescence. Arch Biochem Biophys 46:399–416

    CAS  PubMed  Google Scholar 

  99. Lee RT, McElroy WD (1971) Isolation and partial characterization of a peptide derived from the luciferin binding site of firefly luciferase. Arch Biochem Biophys 146:551–556

    CAS  PubMed  Google Scholar 

  100. Lee RT, Denburg TL, McElroy WD (1970) Substrate-binding properties of firefly luciferase. Arch Biochem Biophys 141:38–52

    CAS  PubMed  Google Scholar 

  101. Ueda I (1965) Effects of diethylether and halothane on firefly luciferin bioluminescence. Anesthesiology 26:603606

    Google Scholar 

  102. Ueda I, Suzuki A (1998) Is there a specific receptor for anesthetics? Contrary effects of alcohols and fatty acids on phase transition and bioluminescence of firefly luciferase. Biophys J 75:1052–1057

    CAS  PubMed  Google Scholar 

  103. Ueda I, Suzuki A (1998) Irreversible phase transition of firefly luciferase: contrasting effects of volatile anesthetics and myristic acid. Biochim Biophys Acta 1380:313–319

    CAS  PubMed  Google Scholar 

  104. Rocha S, Campbell KJ, Roche KC, Perkins ND (2003) The p53-inhibitor pifithrin-α inhibits firefly luciferase activity in vivo and in vitro. BMC Mol Biol 4:1–8

    Google Scholar 

  105. Niwa K, Ohmiya Y (2004) Inhibitory effect of lipoic acid on firefly luciferase bioluminescence. Biochem Biophys Res Commun 323:625–629

    CAS  PubMed  Google Scholar 

  106. Heitman LH, van Veldhoven JP, Zweemer AM, Ye K, Brussee J, IJzerman AP (2008) False positives in a reporter gene assay: Identification and synthesis of substituted N-pyridin-2-ylbenzamides as competitive inhibitors of firefly luciferase. J Med Chem 51:4724–4729

    CAS  PubMed  Google Scholar 

  107. Auld DS, Zhang YQ, Southall NT, Rai G, Landsman M, Maclure J, Langevin D, Thomas CJ, Austin CP, Inglese J (2009) A basis for reduced chemical library inhibition of firefly luciferase obtained from directed evolution. J Med Chem 52:1450–1458

    CAS  Google Scholar 

  108. Auld DS, Southall NT, Jadhav A, Johnson RL, Diller DJ, Simeonov A, Austin CP, Inglese J (2008) Characterization of chemical libraries for luciferase inhibitory activity. J Med Chem 5:2372–2386

    Google Scholar 

  109. Auld DS, Thorne N, Nguyen D-T, Inglese J (2008) A specific mechanism for nonspecific activation in reporter-gene assays. ACS Chem Biol 3:463–470

    CAS  PubMed  Google Scholar 

  110. Green AA, McElroy WD (1956) Crystalline firefly luciferase. Biochim Biophys Acta 20:170–176

    CAS  PubMed  Google Scholar 

  111. Branchini BR, Marschner TM, Montemurro AM (1980) A convenient affinity chromatography-based purification of firefly luciferase. Anal Biochem 104:386–396

    CAS  PubMed  Google Scholar 

  112. Rajgopal S, Vijayalakshmi M (1982) Purification of luciferase by affinity elution chromatography on Blue Dextran columns: comparison of Sepharose and silica as support matrices. J Chromatogr 243:164–167

    CAS  Google Scholar 

  113. Belinga HF, Steghens JP, Collombel C (1995) Firefly luciferase purification using polyethlene glycol and Dyematrex Orange A. J Chromatogr A 695:33–40

    CAS  Google Scholar 

  114. Kajiyama N, Masuda T, Tatsumi H, Nakano E (1992) Purification and characterization of luciferases from fireflies, Luciola cruciata and Luciola lateralis. Biochim Biophys Acta 1120:228–232

    CAS  PubMed  Google Scholar 

  115. Devine JH, Kutuzova GD, Green VA, Ugarova NN, Baldwin TO (1993) Luciferase from the East European firefly Luciola mingrelica: cloning and nucleotide sequence of the cDNA, overexpression in Escherichia coli and purification of the enzyme. Biochim Biophys Acta 1173:121–132

    CAS  PubMed  Google Scholar 

  116. Branchini BR, Magyar RA, Murtiashaw MH, Anderson SM, Zimmer M (1998) Site-directed mutagenesis of histidine 245 in firefly luciferase: a proposed model of the active site. Biochemistry 37:15311–15319

    CAS  PubMed  Google Scholar 

  117. Inouye S, Sahara Y (2008) Soluble protein expression in E. coli cells using IgG binding domain of protein A as a solubilizing partner in the cold induced system. Biochem Biophys Res Commun 376:448–453

    CAS  PubMed  Google Scholar 

  118. de Wet JR, Wood KV, Helinski DR, DeLuca M (1985) Cloning of firefly luciferase cDNA and the expression of active luciferase in Escherichia coli. Proc Natl Acad Sci USA 82:7870–7873

    PubMed  Google Scholar 

  119. de Wet JR, Wood KV, DeLuca M, Helinski DR, Subramani S (1987) Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol 7:725–737

    PubMed  Google Scholar 

  120. Keller GA, Gould S, DeLuca M, Subramani S (1987) Firefly luciferase is targeted to peroxisomes in mammalian cells. Proc Natl Acad Sci USA 84:3264–3268

    CAS  PubMed  Google Scholar 

  121. Cho KH, Lee JS, Choi YD, Boo KS (1999) Structural polymorphism of the luciferase gene in the firefly, Luciola lateralis. Insect Mol Biol 8:193–200

    CAS  PubMed  Google Scholar 

  122. Schröder J (1989) Protein sequence homology between plant 4-coumarate:CoA ligase and firefly luciferase. Nucl Acids Res 17:460

    PubMed  Google Scholar 

  123. Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, Hashimoto T, Yamamoto T (1990) Structure and regulation of rat long-chain acyl-CoA synthetase. J Biol Chem 265:8681–8685

    CAS  PubMed  Google Scholar 

  124. Toh H (1991) Sequence analysis of firefly luciferase family reveals a conservative sequence motif. Protein Seq Data Anal 4:111–117

    CAS  PubMed  Google Scholar 

  125. Ye L, Buck LM, Schaeffer HJ, Leach FR (1997) Cloning and sequencing of a cDNA for firefly luciferase from Photuris pennsylvanica. Biochim Biophys Acta 1339:39–52

    CAS  PubMed  Google Scholar 

  126. Choi YS, Bae JS, Lee KS, Kim SR, Kim I, Kim JG, Kim KY, Kim SE, Suzuki H, Lee SM, Sohn HD, Jin BR (2003) Genomic structure of the luciferase gene and phylogenetic analysis in the Hotaria-group fireflies. Comp Biochem Physiol 134B:199–214

    CAS  Google Scholar 

  127. Conti E, Franks NP, Brick P (1996) Crystal structure of firefly luciferase throws light on superfamily of adenylate-forming enzymes. Structure 4:287–298

    CAS  PubMed  Google Scholar 

  128. Franks NP, Jenkins JE, Conti E, Lieb WR, Brick P (1998) Structural basis for the inhibition of firefly luciferase by a general anesthetic. Biophys J 75:2205–2211

    CAS  PubMed  Google Scholar 

  129. Branchini BR, Murtiashaw MH, Carmody JN, Mygatt EE, Southworth TL (2005) Synthesis of an N-acyl sulfamate analog of luciferyl-AMP: a stable and potent inhibitor of firefly luciferase. Bioorg Med Chem Lett 15:3860–3864

    CAS  PubMed  Google Scholar 

  130. Nakatsu T, Ichiyama S, Hiratake J, Saldanha A, Kobashi N, Sakata K, Kato H (2006) Structural basis for the spectral difference in luciferase bioluminescence. Nature 440:372–376

    CAS  PubMed  Google Scholar 

  131. Oba Y, Sato M, Ojika M, Inouye S (2005) Enzymatic and genetic characterization of firefly luciferase and Drosophila CG6178 as a fatty acyl-CoA synthetase. Biosci Biotechnol Biochem 69:819–828

    CAS  PubMed  Google Scholar 

  132. Oba Y, Ojika M, Inouye S (2004) Characterization of CG6178 gene product with high sequence similarity to firefly luciferase in Drosophila melanogaster. Gene 329:137–145

    CAS  PubMed  Google Scholar 

  133. Oba Y, Tanaka K, Inouye S (2006) Catalytic properties of domain-exchanged chimeric Proteins between firefly luciferase and Drosophila fatty acyl-CoA synthetase CG6178. Biochem Biocsci Biotechnol 70:2739–2744

    CAS  Google Scholar 

  134. Oba Y, Sato M, Ohta Y, Inouye S (2006) Identification of paralogous genes of firefly luciferase in the Japanese firefly, Luciola cruciata. Gene 368:53–60

    CAS  PubMed  Google Scholar 

  135. Oba Y, Sato M, Inouye S (2006) Cloning and characterization of the homologous genes of firefly luciferase in the mealworm beetle, Tenebrio molitor. Insect Mol Biol 15:293–299

    CAS  PubMed  Google Scholar 

  136. Oba Y, Iida K, Ojika M, Inouye S (2008) Orthologous gene of beetle luciferase in non-luminous click beetle, Agrypnus binodulus (Elateridae), encodes a fatty acyl-CoA synthetase. Gene 407:169–175

    CAS  PubMed  Google Scholar 

  137. Oba Y (2009) On the origin of beetle luminescence. In: Meyer-Rochow VB (ed) Bioluminescence in focus. Res Signpost, India, pp 277–290

    Google Scholar 

  138. Oba Y, Iida K, Inouye S (2009) Functional conversion of fatty acyl-CoA synthetase to firefly luciferase by site-directed mutagenesis: a key substitution responsible for luminescence activity. FEBS Lett 583:2004–2008

    CAS  PubMed  Google Scholar 

  139. Masuda T, Tatsumi H, Nakano E (1989) Cloning and sequence analysis of cDNA for luciferase of a Japanese firefly, Luciola cruciata. Gene 77:265–270

    CAS  PubMed  Google Scholar 

  140. Tatsumi H, Kajiyama N, Nakano E (1992) Molecular cloning and expression in Escherichia coli of a cDNA clone encoding luciferase of a firefly, Luciola lateralis. Biochim Biophys Acta 1131:161–165

    CAS  PubMed  Google Scholar 

  141. Zenno S, Shiraishi S, Inouye S, Saigo K (1993) Photuris firefly luciferase gene. Jpn Pat Appl 5-119050

  142. Ohmiya Y, Ohba N, Toh H, Tsuji FI (1995) Cloning, expression and sequence analysis of cDNA for the luciferases from the Japanese fireflies, Pyrocoelia miyako and Hataria parvula. Photochem Photobiol 62:309–313

    CAS  PubMed  Google Scholar 

  143. Lee KS, Park HJ, Bae JS, Goo TW, Kim I, Sohn HD, Jin BR (2001) Molecular cloning and expression of a cDNA encoding the luciferase from the firefly, Pyrocoelia rufa. J Biotechnol 92:9–19

    CAS  PubMed  Google Scholar 

  144. Choi YS, Lee KS, Bae JS, Lee KM, Kim SR, Kim I, Lee SM, Sohn HD, Jin BR (2002) Molecular cloning and expression of a cDNA encoding the luciferase from the firefly, Hotaria unmunsana. Comp Biochem Physiol B Biochem Mol Biol 132:661–670

    PubMed  Google Scholar 

  145. Sala-Newby GB, Thomson CM, Campbell AK (1996) Sequence and biochemical similarities between the luciferases of the glow-worm Lampyris noctiluca and the firefly Photinus pyralis. Biochem J 313:761–767

    CAS  PubMed  Google Scholar 

  146. Alipour BS, Hosseinkhani S, Nikkhah M, Naderi-Manesh H, Chaichi MJ, Osaloo SK (2004) Molecular cloning, sequence analysis, and expression of a cDNA encoding the luciferase from the glow-worm, Lampyris turkestanicus. Biochem Biophys Res Commun 325:215–222

    PubMed  Google Scholar 

  147. Viviani VR, Arnoldi FG, Brochetto-Braga M, Ohmiya Y (2004) Cloning and characterization of the cDNA for the Brazilian Cratomorphus distinctus larval firefly luciferase: similarities with European Lampyris noctiluca and Asiatic Pyrocoelia luciferases. Comp Biochem Physiol B Biochem Mol Biol 139:151–156

    CAS  PubMed  Google Scholar 

  148. Emamzadeh AR, Hosseinkhani S, Sadeghizadeh M, Nikkhah M, Chaichi MJ, Mortazavi M (2006) cDNA cloning, expression and homology modeling of a luciferase from the firefly Lampyroidea maculata. J Biochem Mol Biol 39:578–585

    CAS  PubMed  Google Scholar 

  149. Wood KV, Lam YA, Seliger HH, McElroy WD (1989) Complementary DNA coding click beetle luciferases can elicit bioluminescence of different colors. Science 244:700–702

    CAS  PubMed  Google Scholar 

  150. Viviani VR, Silva AC, Perez GL, Santelli RV, Bechara EJ, Reinach FC (1999) Cloning and molecular characterization of the cDNA for the Brazilian larval click-beetle Pyrearinus termitilluminans luciferase. Photochem Photobiol 70:254–260

    CAS  PubMed  Google Scholar 

  151. Stolz U, Velez S, Wood KV, Wood M, Feder JL (2003) Darwinian natural selection for orange bioluminescent color in a Jamaican click beetle. Proc Natl Acad Sci USA 100:14955–14959

    CAS  PubMed  Google Scholar 

  152. Viviani VR, Bechara EJ, Ohmiya Y (1999) Cloning, sequence analysis, and expression of active Phrixothrix railroad-worms luciferases: relationship between bioluminescence spectra and primary structures. Biochemistry 38:8271–8279

    CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The author is grateful to Dr. A. Nakagawa (Osaka University, Japan) for illustrating the X-ray structure model of firefly luciferase. Also, the author thanks Dr. T. Hosoya (Tokyo Medical and Dental University, Japan) for discussion about luminescence mechanisms.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Satoshi Inouye.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Inouye, S. Firefly luciferase: an adenylate-forming enzyme for multicatalytic functions. Cell. Mol. Life Sci. 67, 387–404 (2010). https://doi.org/10.1007/s00018-009-0170-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-009-0170-8

Keywords

Navigation