Safe use of genetically modified lactic acid bacteria in food. Bridging the gap between consumers, green groups, and industry

Electronic Journal of Biotechnology

Volumn 9, Issue 4, 2006, Pages 1-25

  Sybesma, Wilbert ^a   Hugenholtz, Jeroen ^b   De Vos, Willem M ^c   Smid, Eddy J ^b  

^a TOP INSTITUTE FOOD AND NUTRITION   (Netherlands)

^b NIZO FOOD RESEARCH   (Netherlands)

^c WAGENINGEN UNIVERSITY   (Netherlands)

Author keywords

Genetic modification; Lactic acid bacteria; Legislation; Novel foods; Safety assessment

Indexed keywords

BIOTECHNOLOGY; FOOD PRODUCTS; LAWS AND LEGISLATION; MUTAGENESIS; RISK ASSESSMENT;

GENETIC ALTERATIONS; GENETIC MODIFICATION; GENETICALLY MODIFIED ORGANISMS (GMO); LACTIC ACID BACTERIA; NOVEL FOODS; SAFETY ASSESSMENT;

BACTERIA;

ALLERGENICITY; ANTIBIOTIC RESISTANCE; CONSUMER; CROP PRODUCTION; FOOD INDUSTRY; FOOD INTAKE; FOOD MICROBIOTECHNOLOGY; GENE EXPRESSION; GENETIC ENGINEERING; GENETICALLY MODIFIED FOOD; GENOMICS; LACTIC ACID BACTERIUM; METABOLOMICS; PROTEOMICS; REVIEW; RISK ASSESSMENT; RISK FACTOR; TOXICITY; TRANSCRIPTOMICS;

ANIMALIA; BACTERIA (MICROORGANISMS);

EID: 33747126908     PISSN: 07173458     EISSN: 07173458     Source Type: Journal    
DOI: 10.2225/vol9-issue4-fulltext-12     Document Type: Review

References (122)

1. AARNIKUNNAS, Johannes; VON WEYMARN, Niklas; RONNHOLM, Kent; LEISOLA, Matti and PALVA, Airi. Metabolic engineering of Lactobacillus fermentum for production of mannitol and pure L-lactic acid or pyruvate. Biotechnology and Bioengineering, June 2003, vol. 82, no. 6, p. 653-663.
2. AMARGER, N. Genetically modified bacteria in agriculture. Biochimie, November 2002, vol. 84, no. 11, p. 1061-1072.
3. ARTHUR, Michel; REYNOLDS, Peter and COURVALIN, Patrice. Glycopeptide resistance in enterococci. Trends in Microbiology, October 1996, vol. 4, no. 10, p. 401-407.
4. BAI, Dong-Mei; ZHAO, Xue-Ming; LI, Xin-Gang and XU, Shi-Min. Strain improvement and metabolic flux analysis in the wild-type and a mutant Lactobacillus lactis strain for L(+)-lactic acid production. Biotechnology and Bioengineering, December 2004, vol. 88, no. 6, p. 681-689.
5. BAPTISTA, Marina; DEPARDIEU, Florence; REYNOLDS, Peter; COURVALIN, Patrice and ARTHUR, Michel. Mutations leading to increased levels of resistance to glycopeptide antibiotics in VanB-type enterococci. Molecular Microbiology, July 1997, vol. 25, no. 1, p. 93-105.
6. BONGERS, Roger S.; HOEFNAGEL, Marcel H.N. and KLEEREBEZEM, Michael. High-level acetaldehyde production in Lactococcus lactis by metabolic engineering. Applied and Environmental Microbiology, February 2005, vol. 71, no. 2, p. 1109-1113.
7. BOUCHER, Isabelle; PARROT, Marc; GAUDREAU, Hélène; CHAMPAGNE, Claude P.; VADEBONCOEUR, Christian and MOINEAU, Sylvain. Novel food-grade plasmid vector based on melibiose fermentation for the genetic engineering of Lactococcus lactis. Applied and Environmental Microbiology, December 2002, vol. 68, no. 12, p. 6152-6161.
8. BOUMERDASSI, H.; MONNET, C.; DESMAZEAUD, M. and CORRIEU, G. Isolation and properties of Lactococcus lactis subsp. lactis biovar diacetylactis CNRZ 483 mutants producing diacetyl and acetoin from glucose. Applied and Environmental Microbiology, June 1997, vol. 63, no. 6, p. 2293-2299.
9. BROADBENT, Jeffery R.; GUMMALLA, Sanjay; HUGHES, Joanne E.; JOHNSON, Mark E.; RANKIN, Scott A. and DRAKE, Mary Anne. Overexpression of Lactobacillus casei D-hydroxyisocaproic acid dehydrogenase in cheddar cheese. Applied and Environmental Microbiology, August 2004, vol. 70, no. 8, p. 4814-4820.
10. BRON, Peter A.; HOFFER, Sally M.; VAN SWAM, Iris I.; DE VOS, Willem M. and KLEEREBEZEM, Michiel. Selection and characterization of conditionally active promoters in Lactobacillus plantarum, using alanine racemase as a promoter probe. Applied and Environmental Microbiology, January 2004, vol. 70, no. 1, p. 310-317.
11. nd May, 2003, Washington DC). Communication.
12. BUTCHKO, Harriett H.; TSCHANZ, Christian and KOTSONIS, Frank N. Postmarketing surveillance of food additives. Regulatory Toxicology and Pharmacology, August 1994, vol. 20, no. 1, part. 1, p.105-118.
13. CANTONI, C.; BERSANI, C.; DAMENIS, C. and COMI, G. Biogenic amines in typical Italian dry sausages. Industrie Alimentari, 1994, vol. 33, p. 1239-1243.
14. CHAVES, A.C.S.D.; FERNANDEZ, M.; LERAYER, A.L.S.; MIERAU, I.; KLEEREBEZEM, M. and HUGENHOLTZ, J. Metabolic engineering of acetaldehyde production by Streptococcus thermophilus. Applied and Environmental Microbiology, November 2002, vol. 68, no. 11, p. 5656-5662.
15. CHEIGH, Chan-Ick; PARK, Hoon; CHOI, Hak-Jong and PYUN, Yu-Ryang. Enhanced nisin production by increasing genes involved in nisin Z biosynthesis in Lactococcus lactis subsp. lactis A164. Biotechnology Letters, February 2005, vol. 27, no. 3, p.155-160.
16. Codex Alimentarius. Codex principles and guidelines on foods derived from biotechnology. Codex Alimentarius Commission, 2003. Joint FAO/WHO Food Standards Programme, Food and Agriculture Organisation: Rome. Available from Internet: ftp://ftp.fao.org/codex/Publications/Booklets/Biotech/Biotech_2003e. pdf. 51 pp.
17. CURIC, Mirjana; STUER-LAURIDSEN, Birgitte; RENAULT, Pierre and NILSSON, Dan. A general method for selection of a-acetolactate decarboxylase-deficient Lactococcus lactis mutants to improve diacetyl formation. Applied and Environmental Microbiology, March 1999, vol. 65, no. 3, p. 1202-1206.
18. DAESCHEL, M.A.; ANDERSSON, R.E. and FLEMING, H.P. Microbial ecology of fermenting plant materials. FEMS Microbiology Reviews, 1987, no. 46, p. 357-367.
19. DE RUYTER, Pascalle G.G.A.; KUIPERS, Oscar P.; MEIJER, Wilco C. and DE VOS, Willem M. Food-grade controlled lysis of Lactococcus lactis for accelerated cheese ripening. Nature Biotechnology, October 1997, vol. 15, no. 10, p. 976-979.
20. DE VOS, Willem M. and HUGENHOLTZ, Jeroen. Engineering metabolic highways in lactococci and other lactic acid bacteria. Trends in Biotechnology, February 2004, vol. 22, no. 2, p. 72-79.
21. DE VOS, Willem M. Gene expression systems for lactic acid bacteria. Current Opinion in Microbiology, June 1999, vol. 2, no. 3, p. 289-295.
22. DESMOND, C.; FITZGERALD, G.F.; STANTON, C. and ROSS, R.P. Improved stress tolerance of GroESL-overproducing Lactococcus lactis and probiotic Lactobacillus paracasei NFBC 338. Applied and Environmental Microbiology, October 2004, vol. 70, no. 10, p. 5929-5936.
23. DICKELY, F.; NILSSON, D.; BECH HANSEN, E. and JOHANSEN, E. Isolation of Lactococcus lactis nonsense suppressors and construction of a food-grade cloning vector. Molecular Microbiology, 1995, vol. 15, no. 5, p. 839-847.
24. DJORDJEVIC, G.M.; O'SULLIVAN, D.J.; WALKER, S.A.; CONKLING, M.A. and KLAENHAMMER, T.R. A triggered-suicide system designed as a defense against bacteriophages. Journal of Bacteriology, November 1997, vol. 179, no. 21, p. 6741-6748.
25. DOOLITTLE, W.F.; BOUCHER, Y.; NESBO, C.L.; DOUADY, C.J.; ANDERSSON, J.O. and ROGER, A.J. How big is the iceberg of which organellar genes in nuclear genomes are but the tip? Philosophical Transactions of the Royal Society London B: Biological Sciences, January 2003, vol. 358, no. 1429, p. 39-58.
26. DROGE, Marcus; PUHLER, Alfred and SELBITSCHKA, Werner. Horizontal gene transfer as a biosafety issue: a natural phenomenon of public concern. Journal of Biotechnology, September 1998, vol. 64, no. 1, p. 75-90.
27. EL ATTAR, Aisha; MONNET, Christophe and CORRIEU. Georges. Metabolism of lactose and citrate by mutants of Lactococcus lactis producing excess carbon dioxide. Journal of Dairy Research, 2000, vol. 67, no. 4, p. 571-583.
28. European Commission (EU). Commission Recommendation 97/618/EC of 29 July 1997 concerning the scientific aspects and the presentation of information necessary to support applications for the placing on the market of novel foods and novel food ingredients and the preparation of initial assessment reports under Regulation (EC) No 258/97.
29. European Commission (EU). Council Directive 2001/18/EC of 12 March 2001 on the deliberate release into the environment of genetically modified organisms (repealing Council Directive 90/220/EC).
30. European Commission (EU). Council Directive 90/219/EC of 23 April 1990 on the contained use of genetically modified micro-organisms.
31. European Commission (EU). Council Directive 98/81/EC of 26 October 1998 amending Directive 90/219/EEC on the contained use of genetically modified micro-organisms.
32. European Commission (EU). On a generic approach to the safety assessment of micro-organisms used in feed/food and feed/food production. Working paper. 2003 [cited January 1, 2006]. Available from Internet: http://europa.eu.int/ comm/food/fs/sc/scf/out178_en.pdf.
33. European Commission (EU). Questions and answers on the regulation of GMOs in the EU, MEMO/02/160 - REV., 4 March 2003. [cited January 1, 2006]. Available from Internet: http://ec.europa.eu/dgs/health_consumer/library/press/ press298_en.pdf.
34. European Commission (EU). Regulation (EC) No 1829/2003 of 22 September 2003 on genetically modified food and feed.
35. European Commission (EU). Regulation (EC) No 258/97 of 27 January 1997 concerning novel foods and novel food ingredients.
36. European Commission (EU/SANCO). Regulation of the European Parliament and of the Council on Nutrition, Functional and Health Claims Made on Foods. Working document SANCO/1832/2002, 2002. [cited January 1, 2006]. Available from Internet: http://www.foodstandards.gov.uk/multimedia/pdfs/draftregsonclaims.pdf.
37. FAETH, K.P. and RADLER, F. Investigation of the formation of amines by LAB. Untersuchung der Aminbildung bei Milchsaeurebakterien. Wein-Wissenschaft, 1994, vol. 49, p. 11-16.
38. FERNANDEZ, Annabelle; THIBESSARD, Annabelle; BORGES, Frédé ric; GINTZ, Brigitte; DECARIS, Bernard and LEBLOND-BOURGET, Nathalie. Characterisation of oxidative stress-resistant mutants of Streptococcus thermophilus CNRZ368. Archives of Microbiology, November 2004, vol. 182, no. 5, p. 364-372.
39. FITZSIMONS, A.; HOLS, P.; JORE, J.; LEER, R.J.; O'CONNELL, M. and DELCOUR, J. Development of an amylolytic Lactobacillus plantarum silage strain expressing the Lactobacillus amylovorus α-amylase gene. Applied and Environmental Microbiology, October 1994, vol. 60, no. 10, p. 3529-3535.
40. nd edition, March 21, 2003. [cited January 1, 2006]. Available from Internet: http://europa.eu.int/ comm/public_opinion/archives/eb/ebs_177_en.pdf.
41. GASSON, M. and DE VOS, W.M. Genetics and Biotechnology of Lactic Acid Bacteria. London ; New York, Blackie Academic and Professional, 1994. 316 pp. ISBN 0-75-140098-X.
42. GASSON, M.J. In vivo genetic systems in LAB. FEMS Microbiology Reviews, September 1990, vol. 7, no. 1-2, p. 43-60.
43. GENEREUX, Diane P. and LOGSDON, John M.JR. Much ado about bacteria-to-vertebrate lateral gene transfer. Trends in Genetics, April 2003, vol. 19, no. 4, p.191-195.
44. GERMOND, Jacques-Edouard; DELLEY, Michèle; D'AMICO, Nicola and VINCENT, Sébastien. Heterologous expression and characterization of the exopolysaccharide from Streptococcus thermophilus Sfi39. European Journal of Biochemistry, October 2001, vol. 268, no. 19, p. 5149-5156.
45. GOUPIL, N.; CORTIER, G.; EHRLICH, S. D. and RENAULT, P. Imbalance of leucine flux in Lactococcus lactis and its use for the isolation of diacetyl-overproducing strains. Applied and Environmental Microbiology, July 1996, vol. 62, no. 7, p. 2636-2640.
46. Health Council of the Netherlands. Safety assessment of novel foods. The Hague: Health Council of the Netherlands, 2002; publication no. 2002/05VNV. [cited 1 January, 2006]. Available from Internet: http://www.gr.nl/pdf.php?ID= 518. ISBN: 90-5549-450-X.
47. HENRIKSEN, Claus Maxel; NILSSON, Dan; HANSEN, Sven and JOHANSEN, Eric. Industrial applications of genetically modified micro-organisms: gene technology at Chr. Hansen A/S. International Dairy Journal, January 1999, vol. 9, no. 1, p. 17-23.
48. HILL, C.; PIERCE, K. and KLAENHAMMER, T.R. The conjugative plasmid pTR2030 encodes two bacteriophage defense mechanisms in lactococci, restriction modification (R+/M+) and abortive infection (Hsp+) Applied and Environmental Microbiology, September 1989, vol. 55, no. 9, p. 2416-2419.
49. HILLMAN, Jeffrey D. Genetically modified Streptococcus mutans for the prevention of dental caries. Antonie Van Leeuwenhoek, August 2002, vol. 82, no. 1-4, p. 361-366.
50. HOLS, Pascal; KLEEREBEZEM, Michiel; SCHANCK, André N.; FERAIN, Thierry; HUGENHOLTZ, Jeroen; DELCOUR, Jean and DE VOS, Willem M. Conversion of Lactococcus lactis from homolactic to homoalanine fermentation through metabolic engineering. Nature Biotechnology, June 1999, vol. 17, no. 6, p. 588-592.
51. HORN, Nikki; MARTINEZ, María I.; MARTINEZ, José M.; HERNANDEZ, Pablo E.; GASSON, Michael J.; RODRIGUEZ, Juan M. and DODD, Helen M. Enhanced production of pediocin PA-1 and coproduction of nisin and pediocin PA-1 by Lactococcus lactis. Applied and Environmental Microbiology, October 1999, vol. 65, no. 10, p. 4443-4450.
52. HUGENHOLTZ, J. and DE VEER, G.J.M. Application of nisin A and nisin Z in dairy technology. In: JUNG, G. and SAHL, H. eds. Nisin and Novel Lantibiotics. ESCOM Science Publishers, Leiden, 1991, p. 440-447.
53. IBRAHIM, S.A. and O'SULLIVAN, D.J. Use of chemical mutagenesis for the isolation of food grade beta-galactosidase overproducing mutants of bifidobacteria, lactobacilli and Streptococcus thermophilus. Journal of Dairy Science, May 2000, vol. 83, no. 5, p. 923-930.
54. JAIN, Ravi; RIVERA, Maria C.; MOORE, Jonathan E. and LAKE, James A. Horizontal gene transfer in microbial genome evolution. Theoretical Population Biology, June 2002, vol. 61, no. 4, p. 489-495.
55. JANY, K.-D. and SCHUH, S. Die neuen EU-Verordnungen Nr. 1829/2003 und Nr. 1830/2003 zu genetisch veränderten Lebens und Futtermittlen: die Kennzeichnung. Journal für Ernährungsmedizin, 2005, vol. 7, no. 2, p. 6-12.
56. JOUTSJOKI, V.; LUOMA, S.; TAMMINEN, M.; KILPI, M.; JOHANSEN, E. and PALVA, A. Recombinant Lactococcus starters as a potential source of additional peptidolytic activity in cheese ripening. Journal of Applied Microbiology, June 2002, vol. 92, no. 6, p.1159-1166.
57. KATAN, Martijn B. and DE ROOS, Nicole M. Toward Evidence-Based Health Claims for Foods. Science, January 2003, vol. 299, no. 5604, p. 206-207.
58. KEROVUO, J. and TYNKKYNEN, S. Expression of Bacillus subtilis phytase in Lactobacillus plantarum 755. Letters in Applied Microbiology, April 2000, vol. 30, no. 4, p. 325-329.
59. KIM, Jeong Hwan; KIM, Sung Guk; CHUNG, Dae Kyun; BOR, Yeou-Cherng and BATT, Carl A. Use of antisense RNA to confer bacteriophage resistance in dairy starter cultures. Journal of Industrial Microbiology and Biotechnology, August 1992, vol. 10, no. 2, p. 71-78.
60. KLEEREBEZEM, M.; BEERTHUYZEN, M.M.; VAUGHAN, E.E; DE VOS, W.M. and KUIPERS, O.P. Controlled gene expression systems for lactic acid bacteria: transferable nisin-inducible expression cassettes for Lactococcus, Leuconostoc, and Lactobacillus spp. Applied and Environmental Microbiology, November 1997, vol. 63, no. 11, p. 4581-4584.
61. nd June, 2000, Geneva, Rome, Italy). Food and Agriculture Organisation of the United Nations. Available from Internet: ftp://ftp.fao.org/es/esn/food/Bio-12.pdf.
62. KUIPER, Harry A.; KLETER, Gijs A.; NOTEBORN, Hub P.J.M. and KOK, Esther J. Assessment of the food safety issues related to genetically modified foods. The Plant Journal, September 2001, vol. 27, no. 6, p. 503-528.
63. KYLA-NIKKILA, Kari; HUJANEN, Mervi; LEISOLA, Matti and PALVA, Airi. Metabolic engineering of Lactobacillus helveticus CNRZ32 for production of pure L-(+)-lactic acid. Applied and Environmental Microbiology, September 2000, vol. 66, no. 9, p. 3835-3841.
64. LAPIERRE, Luciane; GERMOND, Jacques-Edouard; OTT, Andreas; DELLEY, Michele and MOLLET, Beat. D-Lactate dehydrogenase gene (ldhD) inactivation and resulting metabolic effects in the Lactobacillus johnsonii strains La1 and N312. Applied and Environmental Microbiology, September 1999, vol. 65, no. 9, p. 4002-4007.
65. LEA, Linda. Phytosterol-esters. Use in a range of food products. Safety and Environmental Assurance Centre, Unilever Colworth, Sharnbrook, UK. Document reference: D02-018. 2002.
66. LEENHOUTS, K.; BUIST, G.; BOLHUIS, A.; TEN BERGE, A.; KIEL, J.; MIERAU, I.; DABROWSKA, M.; VENEMA, G. and KOK, J. A general system for generating unlabelled gene replacements in bacterial chromosomes. Molecular and General Genetics, November 1996, vol. 253, no. 1-2, p. 217-224.
67. LEISNER, Jorgen J. Weeds, heat and pure cultures - On the differential success of new technologies in the Danish and American creamery industries in the 1890s. Food Policy, August 2005, vol. 30, no. 4, p. 419-433.
68. LEVANDER, Fredrik; SVENSSON, Malin and RADSTROM, Peter. Enhanced exopolysaccharide production by metabolic engineering of Streptococcus thermophilus. Applied and Environmental Microbiology, February 2002, vol. 68, no. 2, p. 784-790.
69. LI, Yin; HUGENHOLTZ, Jeroen; SYBESMA, Wilbert; ABEE, Tjakko and MOLENAAR, Douwe. Using Lactococcus lactis for glutathione overproduction. Applied Microbiology and Biotechnology, April 2005, vol. 67, no. 1, p. 83-90.
70. LIU, Ying; EKAMBARAM, Meenakshi C.; BLUM, Penny S.; STIMBERT, Cynthia D. and JERNIGAN JR, Howard M. Galactosemic cataractogenesis disrupts intracellular interactions and changes the substrate specificity of choline/ethanolamine kinase. Experimental Eye Research, August 1998, vol. 67, no. 2, p. 193-202.
71. LU, Z.; BREIDT, F.; PLENGVIDHYA, V. and FLEMING, H.P. Bacteriophage ecology in commercial sauerkraut fermentations. Applied and Environmental Microbiology, June 2003, vol. 69, no. 6, p. 3192-3202.
72. MACCORMICK, Caroline A.; GRIFFIN, Hugh G. and GASSON, Michael J. Construction of a food-grade host/vector system for Lactococcus lactis based on the lactose operon. FEMS Microbiology Letters, March 1995, vol. 127, no. 1-2, p. 105-109.
73. MADSEN, Soren M.; ARNAU, José; VRANG, Astrid; GIVSKOV, Michael and ISRAELSEN, Hans. Molecular characterization of the pH-inducible and growth phase-dependent promoter P170 of Lactococcus lactis. Molecular Microbiology, April 1999, vol. 32, no. 1, p. 75-87.
74. MAGUIN, E.; PREVOST, H.; EHRLICH, S.D. and GRUSS, A. Efficient insertional mutagenesis in lactococci and other gram-positive bacteria. Journal of Bacteriology, February 1996, vol. 178, no. 3, p. 931-935.
75. MATHIESEN, G.; SORVIG, E.; BLATNY, J.; NATERSTAD, K.; AXELSSON, L. and EIJSINK, V.G.H. High-level gene expression in Lactobacillus plantarum using a pheromone-regulated bacteriocin promoter. Letters in Applied Microbiology, August 2004, vol. 39, no. 2, p. 137-143.
76. MERCENIER, Annick; MULLER-ALOUF, H. and GRANGETTE, Corinne. Lactic acid bacteria as live vaccines. Current Issues in Molecular Biology, 2000, vol. 2, no. 1, p.17-25.
77. MIERAU, Igor; LEIJ, Peter; VAN SWAM, Iris; BLOMMESTEIN, Barry; FLORIS, Esther; MOND, James and SMID, Eddy J. Industrial-scale production and purification of a heterologous protein in Lactococcus lactis using the nisin-controlled gene expression system NICE: The case of lysostaphin. Microbial Cell Factories, May 2005, vol. 4, p. 15.
78. MILLS, S.; COFFEY, A.; O'SULLIVAN, L.; STOKES, D.; HILL, C.; FITZGERALD, G.F. and ROSS, R.P. Use of lacticin 481 to facilitate delivery of the bacteriophage resistance plasmid, pCBG104 to cheese starters. Journal of Applied Microbiology, February 2002, vol. 92, no. 2, p. 238-246.
79. MOLLET, B. and DELLEY, M. Spontaneous deletion formation within the β-galactosidase gene of Lactobacillus bulgaricus. Journal of Bacteriology, October 1990, vol. 172, no. 10, p. 5670-5676.
80. MONNET, Christophe; AYMES, Frédéric and CORRIEU, Georges. Diacetyl and α-acetolactate overproduction by Lactococcus lactis subsp. lactis biovar diacetylactis mutants that are deficient in α-acetolactate decarboxylase and have a low lactate dehydrogenase activity. Applied and Environmental Microbiology, December 2000, vol. 66, no. 12, p. 5518-5520.
81. MONTEVILLE, Marshall; ARDESTANI, Bahram and GELLER, Bruce L. Lactococcal bacteriophages require a host cell wall carbohydrate and a plasma membrane protein for adsorption and ejection of DNA. Applied and Environmental Microbiology, September 1994, vol. 60, no. 9, p. 3204-3211.
82. MORRISSEY, John P.; WALSH, Ultan F.; O'DONNELL, Anne; MOENNE-LOCCOZ, Yvan and O'GARA, Fergal. Exploitation of genetically modified inoculants for industrial ecology applications. Antonie Van Leeuwenhoek, March 2002, vol. 81, no. 1-4, p. 599-606.
83. NAUTA, Arjen; VAN DEN BURG, Bertus; KARSENS, Harma; VENEMA, Gerard and KOK, Jan. Design of thermolabile bacteriophage repressor mutants by comparative molecular modeling. Nature Biotechnology, October 1997, vol. 15, no. 10, p. 980-983.
84. NOVOTNY, René; SCHEBERL, Andrea; GIRYLATERRIERE, Marc; MESSNER, Paul and SCHAFFER, Christina. Gene cloning, functional expression and secretion of the S-layer protein SgsE from Geobacillus stearothermophilus NRS 2004/3a in Lactococcus lactis. FEMS Microbiology Letters, January 2005, vol. 242, no. 1, p. 27-35.
85. NYYSSOLA, Antti; PIHLAJANIEMI, Anne; PALVA, Airi; VON WEYMARN, Niklas and LEISOLA, Matti. Production of xylitol from d-xylose by recombinant Lactococcus lactis. Journal of Biotechnology, July 2005, vol. 118, no. 1, p. 55-66.
86. OECD. Safety evaluation of foods produced by modern biotechnology - concepts and principles. OECD, Paris, 1993.
87. O'SULLIVAN, Lisa; RYAN, Maire P.; ROSS, R. Paul and HILL, Collin. Generation of food-grade lactococcal starters which produce the lantibiotics lacticin 3147 and lacticin 481. Applied and Environmental Microbiology, June 2003, vol. 69, no. 6, p. 3681-3685.
88. PAYNE, John; MACCORMICK, Caroline A.; GRIFFIN, Hugh G. and GASSON, Michael J. Exploitation of a chromosomally integrated lactose operon for controlled gene expression in Lactococcus lactis. FEMS Microbiology Letters, February 1996, vol. 136, no. 1, p. 19-24.
89. nd May, 2003, Washington DC). Communication.
90. PICON, A.; DE TORRES, B.; GAYA, P. and NUNEZ, M. Cheesemaking with a Lactococcus lactis strain expressing a mutant oligopeptide binding protein as starter results in a different peptide profile. International Journal of Food Microbiology, October 2005, vol. 104, no. 3, p. 299-307.
91. PLATTEEUW, C.; VAN ALEN-BOERRIGTER, I.; VAN SCHALKWIJK, S. and DE VOS, W.M. Food-grade cloning and expression system for Lactococcus lactis. Applied and Environmental Microbiology, March 1996, vol. 62, no. 3, p. 1008-1013.
92. nd May, 2003, Washington DC). Abstract O-079, p. 481.
93. RENAULT, Pierre. Expression profiles as fingerprints for the safety evaluation of new strains, including GMOs used in bioprocessed food (EXPRESS-FINGERPRINTS). EU funded project, QLK3-2001-01473. 2001.
94. RENAULT, Pierre. Genetically modified lactic acid bacteria: applications to food or health and risk assessment. Biochimie, November 2002, vol. 84, no. 11, p. 1073-1087.
95. RIJNEN, Liesbeth; COURTIN, Pascal; GRIPON, Jean-Claude and YVON, Mireille. Expression of a heterologous glutamate dehydrogenase gene in Lactococcus lactis highly improves the conversion of amino acids to aroma compounds. Applied and Environmental Microbiology, April 2000, vol. 66, no. 4, p. 1354-1359.
96. ROCHAT, Tatiana; GRATADOUX, Jean-Jacques; CORTHIER, Gérard; COQUERAN, Bérard; NADERMACIAS, Maria-Elena; GRUSS, Alexandra and LANGELLA, Philippe. Lactococcus lactis SpOx spontaneous mutants: a family of oxidative-stress-resistant dairy strains. Applied and Environmental Microbiology, May 2005, vol. 71, no. 5, p. 2782-2788.
97. SANDERS, J.W.; VENEMA, G. and KOK, J. A chloride-inducible gene expression cassette and its use in induced lysis of Lactococcus lactis. Applied and Environmental Microbiology, December 1997, vol. 63, no. 12, p. 4877-4882.
98. SCHEIRLINCK, T.; MAHILLON, J.; JOOS, H.; DHAESE, P. and MICHIELS, F. Integration and expression of alpha-amylase and endoglucanase genes in the Lactobacillus plantarum chromosome. Applied and Environmental Microbiology, September 1989, vol. 55, no. 9, p. 2130-2137.
99. SEALE, D.R. Bacterial inoculants as silage additives. Journal of Applied Bacteriology Symposium Supplement, 1986, vol. 61, no. 15, p. 9S-26S.
100. SILVESTRONI, Aurelio; CONNES, Cristelle; SESMA, Fernando; DE GIORI, Graciela Savoy and PIARD, Jean-Christophe. Characterization of the melA locus for α-galactosidase in Lactobacillus Plantarum. Applied and Environmental Microbiology, November 2002, vol. 68, no. 11, p. 5464-5471.
101. SLOUGH, Candice L.; MIDAY, Robert K.; ZORICH, Nora L. and JONES, Judith K. Postmarketing surveillance of new food ingredients: design and implementation of the program for the fat replacer olestra. Regulatory Toxicology and Pharmacology, April 2001, vol. 33, no. 2, p. 218-223.
102. SOLEM, Christian and JENSEN, Peter Ruhdal. Modulation of gene expression made easy. Applied and Environmental Microbiology, May 2002, vol. 68, no. 5, p. 2397-2403.
103. STEIDLER, Lothar; NEIRYNCK, Sabine; HUYGHEBAERT, Nathalie; SNOECK, Veerle; VERMEIRE, An; GODDEERIS, Bruno; COX, Eric; REMON, Jean Paul and REMAUT, Erik. Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nature Biotechnology, July 2003, vol. 21, no. 7, p. 785-789.
104. STINGELE, Francesca; VINCENT, Sébastien; FABER, Elisabeth; NEWELL, John W.; KAMERLING, Johannis P. and NEESER, Jean-Richard. Introduction of the exopolysaccharide gene cluster from Streptococcus thermophilus Sfi6 into Lactococcus lactis MG1363: production and characterization of an altered polysaccharide. Molecular Microbiology, June 1999, vol. 32, no. 6, p. 1287-1295.
105. STURINO, Joseph M. and KLAENHAMMER, Todd R. Expression of antisense RNA targeted against Streptococcus thermophilus bacteriophages. Applied and Environmental Microbiology, February 2002, vol. 68, no. 2, p. 588-596.
106. SWINDELL, S.R.; BENSON, K.H.; GRIFFIN, H.G.; RENAULT, P.; EHRLICH, S.D. and GASSON, M.J. Genetic manipulation of the pathway for diacetyl metabolism in Lactococcus lactis. Applied and Environmental Microbiology, July 1996, vol. 62, no. 7, p. 2641-2643.
107. SYBESMA, Wilbert; STARRENBURG, Marjo; KLEEREBEZEM, Michiel; MIERAU, Igor; DE VOS, Willem M.; VAN DEN BORN, Erwin and HUGENHOLTZ, Jeroen. Controlled modulation of folate polyglutamyl tail length by metabolic engineering of Lactococcus lactis. Applied and Environmental Microbiology, December 2003a, vol. 69, no. 12, p. 7101-7107.
108. SYBESMA, Wilbert; STARRENBURG, Marjo; KLEEREBEZEM, Michiel; MIERAU, Igor; DE VOS, Willem M. and HUGENHOLTZ, Jeroen. Increased production of folate by metabolic engineering of Lactococcus lactis. Applied and Environmental Microbiology, June 2003b, vol. 69, no. 6, p. 3069-3076.
109. TAKALA, T.; SARIS, P. and TYNKKYNEN, S. Food-grade host/vector expression system for Lactobacillus casei based on complementation of plasmid-associated phospho-beta-galactosidase gene lacG. Applied Microbiology and Biotechnology, January 2003, vol. 60, no. 5, p. 564-570.
110. TANGNEY, Mark and FITZGERALD, Gerald F. AbiA, a lactococcal abortive infection mechanism functioning in Streptococcus thermophilus. Applied and Environmental Microbiology, December 2002, vol. 68, no. 12, p. 6388-6391.
111. TEN BRINK, B.; DAMINK, C.; JOOSTEN, H.M.L.J. and HUIS IN 'T VELD, J.H.J. Occurrence and formation of biologically active amines in foods. International Journal of Food Microbiology, August 1990, vol. 11, no. 1, p. 73-84.
112. TEUBER, Michael; MEILE, Leo and SCHWARZ, Franziska. Acquired antibiotic resistance in LAB from food. Antonie Van Leeuwenhoek, November 1999, vol. 76, no. 1-4, p. 115-137.
113. THOMPSON, J.; CHASSY, B.M. and EGAN, W. Lactose metabolism in Streptococcus lactis: studies with a mutant lacking glucokinase and mannose-phosphotransferase activities. Journal of Bacteriology, April 1985, vol. 162, no. 1, p. 217-223.
114. VAUGHAN, Elaine E.; VAN DEN BOGAARD, Patrick; CATZEDDU, Pasquale; KUIPERS, Oscar P. and DE VOS, Willem M. Activation of silent gal genes in the lac-gal regulon of Streptococcus thermophilus. Journal of Bacteriology, February 2001, vol. 183, no. 4, p. 1184-1194.
115. VISSER, J. Arjan G.M.; AKKERMANS, Antoon D.L.; HOEKSTRA, Rolf F. and DE VOS, Willem M. Insertion-sequence-mediated mutations isolated during adaptation to growth and starvation in Lactococcus lactis. Genetics, November 2004, vol. 168, no. 3, p. 1145-1157.
116. VON WRIGHT, Atte and BRUCE, Ake. Genetically modified micro-organisms and their potential effects on human health and nutrition. Trends in Food Science and Technology, May-August 2003, vol.14, no. 5-8, p. 264-276.
117. WALKER, Shirley and KLAENHAMMER, Todd R. Molecular characterization of a phage-inducible middle promoter and its transcriptional activator from the lactococcal bacteriophage phi31. Journal of Bacteriology, February 1998, vol. 180, no. 4, p. 921-931.
118. WEGKAMP, Arno; STARRENBURG, Marjo; DE VOS, Willem M.; HUGENHOLTZ, Jeroen and SYBESMA, Wilbert. Transformation of folate-consuming Lactobacillus gasseri into a folate producer. Applied and Environmental Microbiology, May 2004, vol. 70, no. 5, p. 3146-3148.
119. WEGMANN, U.; KLEIN, J.R.; DRUMM, I.; KUIPERS, O.P. and HENRICH, B. Introduction of peptidase genes from Lactobacillus delbrueckii subsp. lactis into Lactococcus lactis and controlled expression. Applied and Environmental Microbiology, November 1999, vol. 65, no. 11, p. 4729-4733.
120. WELMAN, A.D.; MADDOX, I.S. and ARCHER, R.H. Screening and selection of exopolysaccharide-producing strains of Lactobacillus delbrueckii subsp. Bulgaricus. Journal of Applied Microbiology, December 2003, vol. 95, no. 6, p.1200-1206.
121. WISSELINK, H. Wouter; MOERS, Antoine P.H.A.; MARS, Astrid E.; HOEFNAGEL, Marcel H.N.; DE VOS, Willem M. and HUGENHOLTZ, Jeroen. Overproduction of heterologous mannitol 1-phosphatase: a key factor for engineering mannitol production by Lactococcus lactis. Applied and Environmental Microbiology, March 2005, vol. 71, no. 3, p. 1507-1514.
122. WYMER, Paul. The application of genetically modified lactic acid bacteria in food products in Europe. Workshop Report, Lactic Acid Bacterial Industrial Platform (LABIP). [cited January 20, 2006] 1998. Available from Internet: http://www.labip.com/workshops-docs/worksgmolab.pdf.