Chemistry: molecular biology and microbiology – Vector – per se
Patent
1997-12-29
2000-10-17
Salimi, Ali
Chemistry: molecular biology and microbiology
Vector, per se
4352523, 435 691, 435 911, 4352351, C12N 1500, C12N 700, C12N 120, C12P 1934
Patent
active
06133023&
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
The present invention provides novel lactic acid bacterial regulatable expression systems which are based on modification of naturally occurring regulatory sequences whereby the expression of genes can be modulated to obtain production of gene products at desirable levels. Recombinant lactic acid bacteria comprising such expression systems are useful in the manufacturing of food products, in the production of animal feed or as production strains in the manufacturing of homologous or heterologous gene products, including pharmaceutically or immunologically active gene products. Recombinant lactic acid bacteria expressing antigenic determinants as provided herein are useful as live vaccines.
TECHNICAL BACKGROUND AND PRIOR ART
For centuries, starter cultures of lactic acid bacteria have been used in food production due to their ability to convert sugars by fermentation into organic acids, predominantly lactic acid, and various metabolites associated with the development in the fermented food products of a desirable taste and flavour. Several lactic acid bacteria inherently produce hydrolytic enzymes including peptidases, proteases and lipolytic enzymes, the production of which may e.g. contribute to a desired flavour development in cheeses.
However, for industrial production of a wide range of fermented food products such as all the well-known traditional dairy products including yoghurt, acidophilus milk, butter and cheeses; fermented vegetables; fermented meat products and animal feed, a large range of lactic acid bacterial starter cultures, each being adapted to particular types of food products, are required. Such cultures are presently being selected from naturally occurring strains of lactic acid bacteria on the basis of characteristics such as their ability to ferment sugars present in the food product to be fermented, specific growth temperature requirements, production of desired flavouring compounds, the specific combination of which characteristics renders a specifically selected wildtype culture useful for the production of a particular food product but normally less useful for the production of others.
Obviously, this presently used procedure for developing useful lactic acid bacterial cultures by selection of naturally occurring strains is cumbersome and costly. Furthermore, it has proven difficult to provide starter culture strains which combine all of the required characteristics at an optimal level. Presently, this problem is usually solved by the use of starter cultures comprising a multiplicity of selected lactic acid bacterial strains each having one or several of the characteristics desirable for a particular food product. The necessity to use such mixed cultures will of course add to the costs in the manufacture of lactic acid bacterial starter cultures.
Based on their traditional and long term application in food manufacturing and the fact that they are considered as nonpathogenic, the lactic acid bacteria are generally recognized as safe (GRAS) food ingredients, even if they are present in a fermented food product as live bacteria at a very high number, such as 10.sup.8 to 10.sup.9 per g.
Currently, it is widely recognized that a substantial industrial need exists to find economically and technically more feasible ways of developing improved lactic acid bacteria for use as food or feed starter cultures or for the production of desired gene products including providing lactic acid bacteria which are useful for a wide range of applications. It is evident that recombinant DNA technology may provide the means to meet this need. In this context, it is crucial that lactic acid bacteria for food manufacturing which are developed by introduction of desired genes by use of gene technology can still be recognized as safe for consumption. It is therefore considered by the food industry that it is essential that recombinant lactic acid bacteria essentially contain only DNA of lactic acid bacterial origin including DNA from wildtype extrachromosomal plasmids frequently found
REFERENCES:
patent: 5837509 (1998-11-01), Israelsen et al.
patent: 5853718 (1998-12-01), Molin et al.
Smith, Elements of Molec.Neurobiology, 2nd ed., p. 74-82, 1996.
Darnell et al, Molec.Cell Biology, p. 400-401, 1986.
Israelsen et al, Appl.Envir.Microbiology 61:2540-2547, Jul. 1995.
Andersen et al., "MPB64 Possesses Tuberculosis-Complex-Specific B- and T-Cell Epitopes", Scand. J. Immunol., vol. 34, pp. 365-372, (1991).
Jensen et al., "Minimal Requirements for Exponential Growth of Lactococcus Lactis", Applied and Environmental Microbiology, vol. 59, No. 12, pp. 4363-4366, (19930.
Klausen et al., Characterization of Purified Protein Derivative of Tuberculin by Use of Monoclonal Antibodies: Scand. J. Immunol., vol. 40, pp. 345-349, (1994).
Oettinger et al., "Cloning and B-Cell-Epitope Mapping of MPT64 From Mycobacterium Tuberculosis H37Rv", Infection and Immunity, vol. 62, No. 5, pp. 2058-2064, (1994).
Oettinger et al., "Mapping of the Delayed-Type Hypersensitivity-Inducing Epitope of Secreted Protein MPT64 from Mycobacterium Tuberculosis", Infection and Immunity, vol. 63, No. 12, pp. 4613-4618.
Sorensen et al., Purification and Characterization of a Low-Molecular-Mass T-Cell Antigen Secreted by Infection and Immunity, vol. 63, No. 5, pp. 1710-1717.
Ballester, Selective Advantage of Deletions Enhancing Chloramphenicol Acetyltransferase Gene Expression in Elsevier Science Publishers, Gene, vol. 41, No. 2/3, pp. 153-163.
Z. Alexieva et al., "Chloramphenicol Induction of cat-86 Requires Ribosome Stalling at a Specific Site in the Leader", Proc. Natl. Acad. Sci. USA, vol. 85, May 1988, pp. 3057-3061.
E. Bidnenko et al., "Phage Operon Involved in Sensitivity to the Lactococcus lactis Abortive Infection Mechanism AbiD1", Journal of Bacteriology, Jul. 1995, pp. 3824-3829.
C. Chiaruttini et al., "Gene Organization, Primary Structure and RNA Processing Analysis of a Ribosomal RNA Operon in Lactococcus lactis", J. Mol. Biol., vol. 230, 1993, pp. 57-76.
S. David et al., "Leuconostoc lactis .beta.-Galactosidase is Encoded by Two Overlapping Genes", Journal of Bacteriology, vol. 74, No. 13, Jul. 1992, p. 4475-4481.
P. de Ruyter et al., " Functional Analysis of Promoters in the Nisin Gene Cluster of Lactococcus lactis", Journal of Bacteriology, vol. 178, No. 12, Journal of Bacteriology, Jun. 1996, pp. 3434-3439.
M. Gasson, "Plasmid Complements of Streptococcus lactis NCDO 712 and Other Lactic Streptococci After Protoplast-Induced Curing", Journal of Bacteriology, vol. 154, No. 1, Apr. 1983, p. 1-9.
D. Hanahan, "Studies on Transformation of Escherichia coli with Plasmids", J. Mol. Biol. Vol. 166 1983, pp. 557-580.
H. Holo et al., "High-Frequency Transformation ,by Electroporation, of Lactococcus lactis subsp. cremoris Grown with Glycine in Osmotically Stabilized Media", Applied and Environmental Microbiology, vol. 55, No. 12, Applied Environmental Microbiology, vol. 55, No. 12, Dec. 1989, pp. 3119-3123.
H. Israelsen et al., "Insertion of Tranposon Tn917 Derivatives into the Lactococcus lactis subsp. lactis Chromosome", Applied and Environmental Microbiology, vol. 59, No. 1, Jan. 1993, pp. 21-26.
H. Israelsen et al., "Cloning and Partial Characterization of Regulated Promoters from Lactococcus lactis Tn917-lacZ Integrants with the New Prometer Probe Vector, pAK80", Applied and Environmental Microbiology, vol. 61, No. 7, Jul. 1995, pp. 2540-2547.
E. Johansen et al., "Characterization of Leuconostoc Isolates from Commercial Mixed Strain Mesophilic Starter Cultures", J. Dairy Sci., vol. 75, 1992, pp. 1186-1191.
R. Kiewiet et al., "The Mode of Replication is a Major Factor in Segregational Plasmid Instability in Lactococcus lactis", Applied and Environmental Microbiology, vol. 59, No. 2, Feb. 1993, pp. 358-364.
Y. Le Loir et al., "Direct Screening of Recombinants in Gram-Positive Bacteria Using the Secreted Staphylococcal Nuclease as a Reporter", Journal of Bacteriology, vol. 176, No. 16, Aug. 1994, pp. 5135-5139.
F. L. Macrina et al., "Novel Shuttle Plasmid Vehicles For Esche
Arnau Jose
Israelsen Hans
Johnsen Mads Groenvald
Madsen Soeren Michael
Ravn Peter
Bioteknologisk Institut
Salimi Ali
LandOfFree
Lactic acid bacterial regulatable expression system does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Lactic acid bacterial regulatable expression system, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Lactic acid bacterial regulatable expression system will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-467384