Characterization of the Lactococcus lactis nisin A operon genes nisP, encoding a subtilisin-like serine protease involved in precursor processing, and nisR, encoding a regulatory protein involved in nisin biosynthesis
Open accessAbstract
Biosynthesis of the lantibiotic peptide nisin by Lactococcus lactis NIZO R5 relies on the presence of the conjugative transposon Tn5276 in the chromosome. A 12-kb DNA fragment of Tn5276 including the nisA gene and about 10 kb of downstream DNA was cloned in L. lactis, resulting in the production of an extracellular nisin precursor peptide. This peptide reacted with antibodies against either nisin A or the synthetic leader peptide, suggesting that it consisted of a fully modified nisin with the nisin leader sequence still attached to it. This structure was confirmed by N-terminal sequencing and 1H-nuclear magnetic resonance analysis of the purified peptide. Deletion studies showed that the nisR gene is essential for the production of this intermediate. The deduced amino acid sequence of the nisR gene product indicated that the protein belongs to the family of two-component regulators. The deduced amino acid sequence of NisP, the putative product of the gene upstream of nisR, showed an N-terminal signal sequence, a catalytic domain with a high degree of similarity to those of subtilisin-like serine proteases, and a putative C-terminal membrane anchor. Cell extracts of Escherichia coli overexpressing nisP were able to cleave the nisin precursor peptide, producing active, mature nisin. A similar activation was obtained with whole cells but not with membrane-free extracts of L. lactis strains carrying Tn5276 in which the nisA gene had been inactivated. The results indicate that the penultimate step in nisin biosynthesis is secretion of precursor nisin without cleavage of the leader peptide, whereas the last step is the cleavage of the leader peptide sequence from the fully maturated nisin peptide.
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Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589 · see citing works
DNA sequencing with chain-terminating inhibitors
Sanger, F., Nicklen, S., & Coulson, A. R. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.12.5463 · Cited by 68,572 · see citing works
Raza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,311 · see citing works
Yanisch-Perron, C., Vieira, J., & Messing, J. W. (1985) · Gene · doi:10.1016/0378-1119(85)90120-9 · Cited by 14,868 · see citing works
A comprehensive set of sequence analysis programs for the VAX
Devereux, J., Haeberli, P. E., & Smithies, O. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.1part1.387 · Cited by 14,222 · see citing works
Schägger, H., & von Jagow, G. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90587-2 · Cited by 11,420 · see citing works
Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes
Studier, F. W., & Moffatt, B. A. (1986) · Journal of Molecular Biology · doi:10.1016/0022-2836(86)90385-2 · Cited by 6,372 · see citing works
A new method for predicting signal sequence cleavage sites
von HEIJNE, G. (1986) · Nucleic Acids Research · doi:10.1093/nar/14.11.4683 · Cited by 4,554 · see citing works
Protein phosphorylation and regulation of adaptive responses in bacteria
Stock, J., Ninfa, A. J., & Stock, A. (1989) · Microbiological Reviews · doi:10.1128/mr.53.4.450-490.1989 · Cited by 1,496 · see citing works
Vectors for selective expression of cloned DNAs by T7 RNA polymerase
Rosenberg, A. H., Lade, B. N., Dao-shan, C., Lin, S., Dunn, J. J., & Studier, F. W. (1987) · Gene · doi:10.1016/0378-1119(87)90165-x · Cited by 1,443 · see citing works
Gasson, M. J. (1983) · Journal of Bacteriology · doi:10.1128/jb.154.1.1-9.1983 · Cited by 1,326 · see citing works
Gross, E., & Morell, J. L. (1971) · Journal of the American Chemical Society · doi:10.1021/ja00747a073 · Cited by 607 · see citing works
Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings
Schnell, N. F., Entian, K., Schneider, U., Götz, F., Zähner, H., Kellner, R., & Jung, G. (1988) · Nature · doi:10.1038/333276a0 · Cited by 538 · see citing works
Hurst, A. (1981) · Advances in applied microbiology · doi:10.1016/s0065-2164(08)70342-3 · Cited by 454 · see citing works
Identification and characterization of the lantibiotic nisin Z, a natural nisin variant
Mulders, J. W. M., Boerrigter, I. J., Rollema, H. S., Siezen, R. J., & de Vos, W. M. (1991) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1991.tb16317.x · Cited by 429 · see citing works
Self-citationFischetti, V. A., Pancholi, V., & Schneewind, O. (1990) · Molecular Microbiology · doi:10.1111/j.1365-2958.1990.tb02072.x · Cited by 411 · see citing works
Construction of a vector plasmid family and its use for molecular cloning in Streptococcus lactis
Simon, D. A., & Chopin, A. (1988) · Biochimie · doi:10.1016/0300-9084(88)90093-4 · Cited by 403 · see citing works
Cloning, sequencing, and secretion of Bacillusamyloliquefacienssubtillisin inBacillus subtilis
Wells, J. A., Ferrari, E., Henner, D. J., Estell, D. A., & Chen, E. Y. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.22.7911 · Cited by 350 · see citing works
Buchman, G. W., Banerjee, S., & HANSEN, J. N. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37587-2 · Cited by 344 · see citing works
Siezen, R. J., de Vos, W. M., Leunissen, J. A. M., & Dijkstra, B. W. (1991) · Protein Engineering Design and Selection · doi:10.1093/protein/4.7.719 · Cited by 337 · see citing works
Self-citationPROKARYOTIC SIGNAL TRANSDUCTION MEDIATED BY SENSOR AND REGULATOR PROTEIN PAIRS
Albright, L. M., Huala, E., & Ausubel, F. M. (1989) · Annual Review of Genetics · doi:10.1146/annurev.ge.23.120189.001523 · Cited by 283 · see citing works
Gene cloning and expression in lactic streptococci
de Vos, W. M. (1987) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1987.tb02466.x · Cited by 283 · see citing works
Kaletta, C., & Entian, K. (1989) · Journal of Bacteriology · doi:10.1128/jb.171.3.1597-1601.1989 · Cited by 280 · see citing works
Vuyst, L. D., & Vandamme, E. J. M. C. (1992) · Journal of General Microbiology · doi:10.1099/00221287-138-3-571 · Cited by 276 · see citing works
Wanner, B. L. (1992) · Journal of Bacteriology · doi:10.1128/jb.174.7.2053-2058.1992 · Cited by 264 · see citing works
von HEIJNE, G., & Abrahmsén, L. (1989) · FEBS Letters · doi:10.1016/0014-5793(89)80579-4 · Cited by 260 · see citing works
Epidermin: sequencing of a heterodet tetracyclic 21‐peptide amide antibiotic
Allgaier, H., Jung, G., Werner, R. G., Schneider, U., & Zähner, H. (1986) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1986.tb09933.x · Cited by 252 · see citing works
Analysis of the Genetic Determinant for Production of the Peptide Antibiotic Nisin
Dodd, H. M., Horn, N., & Gasson, M. J. (1990) · Journal of General Microbiology · doi:10.1099/00221287-136-3-555 · Cited by 247 · see citing works
AUGUSTIN, J., Rosenstein, R., Wieland, B., SCHNEIDER, U., Schnell, N. F., Engelke, G., ENTIAN, K., & Götz, F. (1992) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1992.tb16740.x · Cited by 239 · see citing works
Rauch, P. J. G., & de Vos, W. M. (1992) · Journal of Bacteriology · doi:10.1128/jb.174.4.1280-1287.1992 · Cited by 218 · see citing works
Properties of nisin Z and distribution of its gene, nisZ, in Lactococcus lactis
de Vos, W. M., Mulders, J. W. M., Siezen, R. J., Hugenholtz, J., & Kuipers, O. P. (1993) · Applied and Environmental Microbiology · doi:10.1128/aem.59.1.213-218.1993 · Cited by 216 · see citing works
Self-citationGao, F. H., Abee, T., & Konings, W. N. (1991) · Applied and Environmental Microbiology · doi:10.1128/aem.57.8.2164-2170.1991 · Cited by 208 · see citing works
Engelke, G., Gutowski-Eckel, Z., Hammelmann, M., & Entian, K. (1992) · Applied and Environmental Microbiology · doi:10.1128/aem.58.11.3730-3743.1992 · Cited by 204 · see citing works
Nucleotide sequence of the cell wall proteinase gene of Streptococcus cremoris Wg2.
Kok, J., Leenhouts, K. J., Haandrikman, A. J., Ledeboer, A. M., & Venema, G. (1988) · Applied and Environmental Microbiology · doi:10.1128/aem.54.1.231-238.1988 · Cited by 199 · see citing works
Engineering dehydrated amino acid residues in the antimicrobial peptide nisin.
Kuipers, O. P., Rollema, H. S., Yap, W. M., et al. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35771-5 · Cited by 198 · see citing works
Self-citationAnalysis of genes involved in biosynthesis of the lantibiotic subtilin
Klein, C., Kaletta, C., Schnell, N. F., & Entian, K. (1992) · Applied and Environmental Microbiology · doi:10.1128/aem.58.1.132-142.1992 · Cited by 194 · see citing works
Gene expression in Lactococcus lactis
van de Guchte, M., Kok, J., & Venema, G. (1992) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1992.tb04958.x · Cited by 175 · see citing works
Vos, P., Simons, G., Siezen, R. J., & de Vos, W. M. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)80036-9 · Cited by 170 · see citing works
Self-citationVos, P., van Asseldonk, M., van Jeveren, F., Siezen, R. J., Simons, G., & de Vos, W. M. (1989) · Journal of Bacteriology · doi:10.1128/jb.171.5.2795-2802.1989 · Cited by 167 · see citing works
Self-citationGene cloning and expression in lactic streptococci
de Vos, W. M. (1987) · FEMS Microbiology Letters · doi:10.1016/0378-1097(87)90113-3 · Cited by 163 · see citing works
Comeau, D. E., Ikenaka, K., Tsung, K., & Inouye, M. (1985) · Journal of Bacteriology · doi:10.1128/jb.164.2.578-584.1985 · Cited by 160 · see citing works
Analysis of genes involved in the biosynthesis of lantibiotic epidermin
Schnell, N. F., Engelke, G., Augustin, J., et al. (1992) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1992.tb16605.x · Cited by 160 · see citing works
Klein, C., Kaletta, C., & Entian, K. (1993) · Applied and Environmental Microbiology · doi:10.1128/aem.59.1.296-303.1993 · Cited by 155 · see citing works
Nisin biosynthesis genes are encoded by a novel conjugative transposon
Horn, N., Swindell, S. R., Dodd, H. M., & Gasson, M. J. (1991) · Molecular and General Genetics MGG · doi:10.1007/bf00282457 · Cited by 137 · see citing works
A Powerful Inhibitory Substance Produced by Group N Streptococci
Mattick, A. T. R., & Hirsch, A. K. H. (1944) · Nature · doi:10.1038/154551a0 · Cited by 130 · see citing works
Sahl, H., & Brandis, H. J. (1981) · Microbiology · doi:10.1099/00221287-127-2-377 · Cited by 127 · see citing works
van de Ven, F. J. M., van den Hooven, H. W., Konings, R. N. H., et al. (1991) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1991.tb16488.x · Cited by 125 · see citing works
de Vos, W. M., Vos, P., de Haard, H., & Boerrigter, I. (1989) · Gene · doi:10.1016/0378-1119(89)90477-0 · Cited by 121 · see citing works
Self-citationMELOUN, B., Baudyš, M., Kostka, V., Hausdorf, G., Frömmel, C., & Höhne, W. E. (1985) · FEBS Letters · doi:10.1016/0014-5793(85)80775-4 · Cited by 111 · see citing works
Seki, T., Yoshikawa, H., Takahashi, H., & Saito, H. (1987) · Journal of Bacteriology · doi:10.1128/jb.169.7.2913-2916.1987 · Cited by 98 · see citing works
Gasson, M. J. (1984) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1984.tb00176.x · Cited by 97 · see citing works
Steen, M. T., Chung, Y. J., & HANSEN, J. N. (1991) · Applied and Environmental Microbiology · doi:10.1128/aem.57.4.1181-1188.1991 · Cited by 90 · see citing works
Tanaka, T., & KAWATA, M. (1988) · Journal of Bacteriology · doi:10.1128/jb.170.8.3593-3600.1988 · Cited by 80 · see citing works
Chung, Y. J., Steen, M. T., & HANSEN, J. N. (1992) · Journal of Bacteriology · doi:10.1128/jb.174.4.1417-1422.1992 · Cited by 71 · see citing works
Nisin dissipates the proton motive force of the obligate anaerobe Clostridium sporogenes PA 3679
Okereke, A., & Montville, T. J. (1992) · Applied and Environmental Microbiology · doi:10.1128/aem.58.8.2463-2467.1992 · Cited by 68 · see citing works
Jung, G. (1991) · Angewandte Chemie · doi:10.1002/ange.19911030904 · Cited by 57 · see citing works
Anba, J., Bidaud, M., Vasil, M. L., et al. (1990) · Journal of Bacteriology · doi:10.1128/jb.172.8.4685-4689.1990 · Cited by 50 · see citing works
[Subtilin, VI: the structure of subtilin (author's transl)].
Gross, E., Hh, K., & Nebelin, E. (1973) · PubMed · Cited by 45 · see citing works
Rauch, P. J. G., & de Vos, W. M. (1992) · Gene · doi:10.1016/0378-1119(92)90161-h · Cited by 41 · see citing works
Thompson, J. F., Sackett, D. L., & Donkersloot, J. A. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54617-2 · Cited by 34 · see citing works
Production, processing, and engineering of the Lactococcus lactis SK11 proteinase.
de Vos, W. M., Boerrigter, I. J., Vos, P., Bruinenberg, P. M., Siezen, R. J., Dunny, G. M., Cleary, P. P., & McKay, L. L. (1991) · Cited by 9 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Gross E., Kiltz H. H., Nebelin E. Subtilin, VI. Die Struktur des Subtilins. Hoppe Seylers Z Physiol Chem. 1973 Jul;354(7):810–812. [PubMed] [Google Scholar]
Cited by
Sorted by citations
Bacteriocins: Developing innate immunity for food
Cotter, P. D., Hill, C., & Ross, R. P. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1273 · Cited by 2,380 · see citing works
Navarre, W. W., & Schneewind, O. (1999) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.63.1.174-229.1999 · Cited by 1,391 · see citing works
Schmidt, E. W., Nelson, J. T., Rasko, D. A., Sudek, S., Eisen, J. A., Haygood, M. G., & Ravel, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501424102 · Cited by 567 · see citing works
Bacteriocins and their food applications
And, H. C., & Hoover, D. G. (2003) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/j.1541-4337.2003.tb00016.x · Cited by 550 · see citing works
The proteolytic system of lactic acid bacteria
Kok, J., & De Vos, W. M. (1994) · Genetics and Biotechnology of Lactic Acid Bacteria · doi:10.1007/978-94-011-1340-3_4 · Cited by 205 · see citing works
Self-citationPositive role of cell wall anchored proteinase PrtP in adhesion of lactococci
Habimana, O., Le Goff, C., Juillard, V., Bellon-Fontaine, M.-N., Buist, G., Kulakauskas, S., & Briandet, R. (2007) · BMC Microbiology · doi:10.1186/1471-2180-7-36 · Cited by 58 · see citing works
Lactocepin: the cell envelope-associated Endopeptidase of lactococci.
Broadbent, J. R., & Steele, J. L. (2013) · Handbook of Proteolytic Enzymes · doi:10.1016/b978-0-12-382219-2.00703-1 · Cited by 6 · see citing works
- Authors
- van der Meer, J. R., Polman, J., Beerthuyzen, M. M., Siezen, R. J., Kuipers, O. P., & De Vos, W. M.
- Affiliations
- Department of Biophysical Chemistry, Netherlands Institute for Dairy Research (NIZO), Ede.
- Nederlands Instituut Voor Zuivel Oonderzoek (NL)
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 1993-05
- Volume
- 175
- Issue
- 9
- Pages
- 2578-2588
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC204559
- OpenAlex
- W1625709714
- Cited by
- 318
- References
- 62
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 7 · 2022: 3 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 12 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 12 · 2013: 6 · 2012: 10
- FWCI
- 47.41
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Default journal
- Funders
- Noda Institute for Scientific Research
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- nisin A, Lactococcus lactis, lantibiotic biosynthesis, NISP, subtilisin-like protease, NISA, proteolytic activation
- MeSH terms
- Amino Acid Sequence, Antibodies, Bacterial, Bacterial Proteins, Base Sequence, Cloning, Molecular, Escherichia coli, Genes, Bacterial, Genes, Regulator, Membrane Proteins, Molecular Sequence Data, Nisin, Operon, Protein Conformation, Protein Precursors, Protein Processing, Post-Translational, Serine Endopeptidases, Lactococcus lactis, Subtilisins, Transcription Factors, Sequence Homology, Amino Acid, Sequence Analysis, DNA, Protein Sorting Signals
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