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Cited by 312Bacterial Genetics and BiotechnologyProtein purification and stabilityBiochemical and Structural Characterization

Signal. peptides for recombinant protein secretion in bacterial expression systems

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Freudl, Roland·2018·Microbial Cell Factories
DOI 10.1186/s12934-018-0901-3PMC PMC5875014
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Abstract

The secretion of biotechnologically or pharmaceutically relevant recombinant proteins into the culture supernatant of a bacterial expression host greatly facilitates their downstream processing and significantly reduces the production costs. The first step during the secretion of a desired target protein into the growth medium is its transport across the cytoplasmic membrane. In bacteria, two major export pathways, the general secretion or Sec pathway and the twin-arginine translocation or Tat pathway, exist for the transport of proteins across the plasma membrane. The routing into one of these alternative protein export systems requires the fusion of a Sec- or Tat-specific signal peptide to the amino-terminal end of the desired target protein. Since signal peptides, besides being required for the targeting to and membrane translocation by the respective protein translocases, also have additional influences on the biosynthesis, the folding kinetics, and the stability of the respective target proteins, it is not possible so far to predict in advance which signal peptide will perform best in the context of a given target protein and a given bacterial expression host. As outlined in this review, the most promising way to find the optimal signal peptide for a desired protein is to screen the largest possible diversity of signal peptides, either generated by signal peptide variation using large signal peptide libraries or, alternatively, by optimization of a given signal peptide using site-directed or random mutagenesis strategies.

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  1. [1]Schmidt FR Recombinant expression systems in the pharmaceutical industry Appl Microbiol Biotechnol 2004 65 363 372 10.1007/s00253-004-1656-9 15480623 · DOI
  2. [2]Terpe K Overview of bacterial expression systems for heterologous protein production: from molecular and biochemical fundamentals to commercial systems Appl Microbiol Biotechnol 2006 72 211 222 10.1007/s00253-006-0465-8 16791589 · DOI
  3. [3]Quax WJ Merits of secretion of heterologous proteins from industrial microorganisms Folia Microbiol 1997 42 99 103 10.1007/BF02898715 9306652 · DOI
  4. [4]Pohl S Harwood CR Heterologous protein secretion by Bacillus species: from the cradle to the grave Adv Appl Microbiol 2010 73 1 25 10.1016/S0065-2164(10)73001-X 20800757 · DOI
  5. [5]Li W Zhou X Lu P Bottlenecks in the expression and secretion of heterologous proteins in Bacillus subtilis Res Microbiol 2004 155 605 610 10.1016/j.resmic.2004.05.002 15380546 · DOI
  6. [6]Anné J Economou A Bernaerts K Protein secretion in Gram-positive bacteria: from multiple pathways to biotechnology Curr Top Microbiol Immunol 2017 404 267 308 27885530
  7. [7]Morello E Bermudez-Hamaran LG Llull D Sole V Miraglio N Langella P Poquet I Lactococcus lactis, an efficient cell factory for recombinant protein production and secretion J Mol Microbiol Biotechnol 2008 14 48 58 10.1159/000106082 17957110 · DOI
  8. [8]Anné J Vrancken K Van Mellaert L Van Impe J Bernaerts K Protein secretion biotechnology in Gram-positive bacteria with special emphasis on Streptomyces lividans Biochim Biophys Acta 2014 1843 1750 1761 10.1016/j.bbamcr.2013.12.023 24412306 · DOI
  9. [9]Freudl R Beyond amino acids: use of the Corynebacterium glutamicum cell factory for the secretion of heterologous proteins J Biotechnol 2017 258 101 109 10.1016/j.jbiotec.2017.02.023 28238807 · DOI
  10. [10]van Dijl JM Hecker M Bacillus subtilis: from soil bacterium to super-secreting cell factory Microb Cell Fact 2013 12 3 10.1186/1475-2859-12-3 23311580 PMC3564730 · DOI
  11. [12]Rusch SL Kendall DA Interactions that drive Sec-dependent bacterial protein transport Biochemistry 2007 46 9665 9673 10.1021/bi7010064 17676771 PMC2675607 · DOI
  12. [14]Elvekrog MM Walter P Dynamics of co-translational protein targeting Curr Opin Chem Biol 2015 29 79 86 10.1016/j.cbpa.2015.09.016 26517565 PMC4684440 · DOI
  13. [15]Bechtluft P Nouwen N Tans SJ Driessen AJM SecB—a chaperone dedicated to protein translocation Mol BioSyst 2010 6 620 627 10.1039/B915435C 20237639 · DOI
  14. [16]Kusukawa N Yura T Ueguchi C Akiyama Y Ito K Effects of mutations in heat-shock genes groES and groEL on protein export in Escherichia coli EMBO J 1989 8 3517 3521 2573517 PMC401509
  15. [17]Wild J Altman E Yura T Gross CA DnaK and DnaJ heat shock proteins participate in protein export in Escherichia coli Genes Dev 1992 6 1165 1172 10.1101/gad.6.7.1165 1628824 · DOI · Paper page
  16. [18]Herbort M Klein M Manting EH Driessen AJM Freudl R Temporal expression of the Bacillus subtilis secA gene, encoding a central component of the preprotein translocase J Bacteriol 1999 181 493 500 9882663 PMC93403
  17. [19]Lycklama A Nijeholt JA Driessen AJM The bacterial Sec-translocase: structure and mechanism Philos Trans R Soc B. 2012 367 1016 1028 10.1098/rstb.2011.0201 PMC3297432 22411975 · DOI
  18. [20]Tsukazaki T Mori H Echizen Y Ishitani R Fukai S Tanaka T Perederina A Vassylyev DG Kohno T Maturana AD Ito K Nureki O Structure and function of a membrane component SecDF that enhances protein export Nature 2011 474 235 238 10.1038/nature09980 21562494 PMC3697915 · DOI · Paper page
  19. [21]Dalbey RE Wang P van Dijl JM Membrane proteases in the bacterial protein secretion and quality control pathway Microbiol Mol Biol Rev 2012 76 311 350 10.1128/MMBR.05019-11 22688815 PMC3372248 · DOI
  20. [22]Palmer T Berks BC The twin-arginine translocation (Tat) protein export pathway Nat Rev Microbiol 2012 10 483 496 10.1038/nrmicro2814 22683878 · DOI
  21. [23]Sargent F Stanley NR Berks BC Palmer T Sec-independent protein translocation in Escherichia coli. A distinct and pivotal role for the TatB protein J Biol Chem 1999 274 36073 36082 10.1074/jbc.274.51.36073 10593889 · DOI
  22. [24]Simone D Bay DC Leach T Turner RJ Diversity and evolution of bacterial twin arginine translocase protein, TatC, reveals a protein secretion system that is evolving to fit its environmental niche PLoS ONE 2013 8 11 e78742 10.1371/journal.pone.0078742 24236045 PMC3827258 · DOI
  23. [25]Oertel D Schmitz S Freudl R A TatABC-type Tat translocase is required for unimpaired aerobic growth of Corynebacterium glutamicum ATCC13023 PLoS ONE 2015 10 4 e0123413 10.1371/journal.pone.0123413 25837592 PMC4383559 · DOI
  24. [26]Blaudeck N Kreutzenbeck P Müller M Sprenger GA Freudl R Isolation and characterization of bifunctional Escherichia coli TatA mutant proteins that allow efficient Tat-dependent protein translocation in the absence of TatB J Biol Chem 2005 280 3426 3432 10.1074/jbc.M411210200 15557327 · DOI
  25. [27]Jongbloed JDH van der Ploeg R van Dijl JM Bifunctional TatA subunits in minimal Tat protein translocases Trends Microbiol 2006 14 2 4 10.1016/j.tim.2005.11.001 16303306 · DOI
  26. [28]Alami M Lüke I Deitermann S Eisner G Koch HG Brunner J Müller M Differential interaction between a twin-arginine signal peptide and its translocase in Escherichia coli Mol Cell 2003 12 937 946 10.1016/S1097-2765(03)00398-8 14580344 · DOI
  27. [29]Lausberg F Fleckenstein S Kreutzenbeck P Fröbel J Rose P Müller M Freudl R Genetic evidence for a tight cooperation of TatB and TatC during productive recognition of twin-arginine (Tat) signal peptides in Escherichia coli PLoS ONE 2012 7 6 e39867 10.1371/journal.pone.0039867 22761916 PMC3383694 · DOI
  28. [30]Mori H Cline K A twin arginine signal peptide and the pH gradient trigger reversible assembly of the thylakoid ΔpH/Tat translocase J Cell Biol 2002 157 205 210 10.1083/jcb.200202048 11956224 PMC2199252 · DOI
  29. [31]Gohlke U Pullan L McDevitt CA Porcelli I de Leeuw E Palmer T Saibil HR Berks BC The TatA component of the twin-arginine protein transport system forms channel complexes of variable diameter Proc Natl Acad Sci USA 2005 102 10482 10486 10.1073/pnas.0503558102 16027357 PMC1180781 · DOI
  30. [32]Brüser T Sanders C An alternative model of the twin arginine translocation system Microbiol Res 2003 158 7 17 10.1078/0944-5013-00176 12608575 · DOI
  31. [33]Lüke I Hanford JI Palmer T Sargent F Proteolytic processing of Escherichia coli twin-arginine signal peptides by LepB Arch Microbiol 2009 191 919 925 10.1007/s00203-009-0516-5 19809807 · DOI
  32. [34]Inouye S Soberon X Franceschini T Nakamura K Itakura K Inouye M Role of positive charge on the amino-terminal region of the signal peptide in protein secretion across the membrane Proc Natl Acad Sci USA 1982 79 3438 3441 10.1073/pnas.79.11.3438 7048305 PMC346435 · DOI
  33. [35]Chou MM Kendall DA Polymeric sequences reveal a functional interrelationship between hydrophobicity and length of a signal peptide J Biol Chem 1990 265 2873 2880 2154463
  34. [36]Goldstein J Lehnhardt S Inouye M In vivo effect of asparagine in the hydrophobic region of the signal sequence J Biol Chem 1991 266 14413 14417 1860848
  35. [37]von Heijne G How signal sequences maintain cleavage specificity J Mol Biol 1984 173 243 251 10.1016/0022-2836(84)90192-X 6423828 · DOI
  36. [38]Karamyshev AL Karamysheva ZN Kajava AV Ksenzenko VN Nesmeyanova MA Processing of Escherichia coli alkaline phosphatase: role of the primary structure of the signal peptide cleavage region J Mol Biol 1998 277 859 870 10.1006/jmbi.1997.1617 9545377 · DOI
  37. [39]Berks BC A common export pathway for proteins binding complex redox cofactors ? Mol Microbiol 1996 22 393 404 10.1046/j.1365-2958.1996.00114.x 8939424 · DOI
  38. [40]Cristobal S de Gier JW Nielsen H von Heijne G Competition between Sec- and TAT-dependent protein translocation in Escherichia coli EMBO J 1999 18 2982 2990 10.1093/emboj/18.11.2982 10357811 PMC1171380 · DOI
  39. [41]Blaudeck N Kreutzenbeck P Freudl R Sprenger GA Genetic analysis of pathway specificity during posttranslational protein translocation across the Escherichia coli plasma membrane J Bacteriol 2003 185 2811 2819 10.1128/JB.185.9.2811-2819.2003 12700260 PMC154414 · DOI
  40. [42]Caccia D Dugo M Callari M Bongarzone I Bioinformatics tools for secretome analysis Biochim Biophys Acta 2013 1834 2442 2453 10.1016/j.bbapap.2013.01.039 23395702 · DOI
  41. [43]Käll L Krogh A Sonnhammer ELL A combined transmembrane topology and signal peptide prediction method J Mol Biol 2004 338 1027 1036 10.1016/j.jmb.2004.03.016 15111065 · DOI
  42. [44]Reynolds SM Käll L Riffle ME Bilmes JA Noble WS Transmembrane topology and signal peptide prediction using dynamic Bayesian networks PLoS Comput Biol. 2008 4 e1000213 10.1371/journal.pcbi.1000213 18989393 PMC2570248 · DOI
  43. [46]Bendtsen JD Nielsen H Widdick D Palmer T Brunak S Prediction of twin-arginine signal peptides BMC Bioinform 2005 6 167 10.1186/1471-2105-6-167 PMC1182353 15992409 · DOI
  44. [47]Dilks K Rose R Wesley Hartmann E Pohlschröder M Prokaryotic utilization of the twin-arginine translocation pathway: a genomic survey J Bacteriol 2003 185 1478 1483 10.1128/JB.185.4.1478-1483.2003 12562823 PMC142874 · DOI
  45. [48]Bagos PG Nikolaou EP Liakopoulos TD Tsirigos KD Combined prediction of Tat and Sec signal peptides with hidden Markov models Bioinformatics 2010 26 2811 2817 10.1093/bioinformatics/btq530 20847219 · DOI
  46. [49]Natale P Brüser T Driessen AJM Sec- and Tat-mediated protein secretion across the bacterial cytoplasmic membrane—distinct translocases and mechanisms Biochim Biophys Acta 2008 1778 1735 1756 10.1016/j.bbamem.2007.07.015 17935691 · DOI
  47. [50]Park S Liu G Topping TB Cover WH Randall LL Modulation of folding pathway of exported proteins by the leader sequence Science 1988 239 1033 1035 10.1126/science.3278378 3278378 · DOI
  48. [51]Liu G Topping TB Randall LL Physiological role during export for the retardation of folding by the leader peptide of maltose-binding protein Proc Natl Acad Sci USA 1989 86 9213 9217 10.1073/pnas.86.23.9213 2687876 PMC298464 · DOI
  49. [52]Zalucki YM Beacham IR Jennings MP Biased codon usage in signal peptides: a role in protein export Trends Microbiol 2009 17 146 150 10.1016/j.tim.2009.01.005 19307122 · DOI · Paper page
  50. [53]Zalucki YM Jennings MP Experimental confirmation of a key role for non-optimal codons in protein export Biochem Biophys Res Commun 2007 355 143 148 10.1016/j.bbrc.2007.01.126 17291454 · DOI
  51. [54]Zalucki YM Gittins KL Jennings MP Secretory signal sequence non-optimal codons are required for expression and export of beta-lactamase Biochem Biophys Res Commun 2008 366 135 141 10.1016/j.bbrc.2007.11.093 18053805 · DOI
  52. [55]Gouridis G Karamanou S Gelis I Kalodimos CG Economou A Signal peptides are allosteric activators of the protein translocase Nature 2009 462 363 367 10.1038/nature08559 19924216 PMC2823582 · DOI
  53. [56]Deana A Ehrlich R Reiss C Silent mutations in the Escherichia coli ompA leader peptide region strongly affect transcription and translation in vivo Nucleic Acids Res 1998 26 4778 4782 10.1093/nar/26.20.4778 9753749 PMC147888 · DOI
  54. [57]Punginelli C Ize B Stanley NR Stewart V Sawers G Berks BC Palmer T mRNA secondary structure modulates translation of Tat-dependent formate dehydrogenase N J Bacteriol 2004 186 6311 6315 10.1128/JB.186.18.6311-6315.2004 15342602 PMC515163 · DOI
  55. [58]Brockmeier U Caspers M Freudl R Jockwer A Noll T Eggert T Systematic screening of all signal peptides from Bacillus subtilis: a powerful strategy in optimizing heterologous protein secretion in Gram-positive bacteria J Mol Biol 2006 362 393 402 10.1016/j.jmb.2006.07.034 16930615 · DOI
  56. [59]Mathiesen G Sveen A Brurberg MB Fredriksen L Axelsson L Eijsink VGH Genome-wide analysis of signal peptide functionality in Lactobacillus plantarum WCFS1 BMC Genomics. 2009 10 425 10.1186/1471-2164-10-425 19744343 PMC2748100 · DOI
  57. [60]Degering C Eggert T Puls M Bongaerts J Evers S Maurer KH Jaeger KE Optimization of protease secretion in Bacillus subtilis and Bacillus licheniformis by screening of homologous and heterologous signal peptides Appl Environ Microbiol 2010 76 6370 6376 10.1128/AEM.01146-10 20709850 PMC2950444 · DOI
  58. [61]Watanabe K Tsuchida Y Okibe N Teramoto H Suzuki N Inui M Yukawa H Scanning the Corynebacterium glutamicum R genome for high-efficiency secretion signal sequences Microbiology (UK) 2009 155 741 750 10.1099/mic.0.024075-0 19246745 · DOI
  59. [62]Hemmerich J Rohe P Kleine B Jurischka S Wiechert W Freudl R Oldiges M Use of a Sec signal peptide library from Bacillus subtilis for the optimization of cutinase secretion in Corynebacterium glutamicum Microb Cell Fact 2016 15 208 10.1186/s12934-016-0604-6 27927208 PMC5142396 · DOI
  60. [63]Zhang W Yang M Yang Y Zhan J Zhou Y Zhao X Optimal secretion of alkali-tolerant xylanase in Bacillus subtilis by signal peptide screening Appl Microbiol Biotechnol 2016 100 8745 8756 10.1007/s00253-016-7615-4 27225471 · DOI
  61. [64]Cai D Wei X Qiu Y Chen Y Chen J Wen Z Chen S High-level expression of nattokinase in Bacillus licheniformis by manipulating signal peptide and signal peptidase J Appl Microbiol 2016 121 704 712 10.1111/jam.13175 27159567 · DOI
  62. [65]Tsuji S Tanaka K Takenaka S Yoshida K Enhanced secretion of natto phytase by Bacillus subtilis Biosci Biotechnol Biochem 2016 79 1906 1914 10.1080/09168451.2015.1046366 26023739 · DOI
  63. [66]Mathiesen G Sveen A Piard JC Eijsink VGH Heterologous protein secretion by Lactobacillus plantarum using homologous signal peptides J Appl Microbiol 2008 105 215 226 10.1111/j.1365-2672.2008.03734.x 18298538 · DOI
  64. [67]Meissner D Vollstedt A van Dijl JM Freudl R Comparative analysis of twin-arginine (Tat)-dependent protein secretion of a heterologous model protein (GFP) in three different Gram-positive bacteria Appl Microbiol Biotechnol 2007 76 633 642 10.1007/s00253-007-0934-8 17453196 · DOI
  65. [68]Lammertyn E Desmyter S Schacht S Van Mellaert L Anné L Influence of charge variation in the Streptomyces venezuelae α-amylase signal peptide on heterologous protein production by Streptomyces lividans Appl Microbiol Biotechnol 1998 49 424 430 10.1007/s002530051193 9615485 · DOI
  66. [69]Faß SH Engels JW Influence of specific signal peptide mutations on the expression and secretion of the α-amylase inhibitor tendamistat in Streptomyces lividans J Biol Chem 1996 271 15244 15252 10.1074/jbc.271.25.15244 8662986 · DOI
  67. [70]Caspers M Brockmeier U Degering C Eggert T Freudl R Improvement of Sec-dependent secretion of a heterologous model protein in Bacillus subtilis by saturation mutagenesis of the N-domain of the AmyE signal peptide Appl Microbiol Biotechnol 2010 86 1877 1885 10.1007/s00253-009-2405-x 20077115 · DOI
  68. [71]Sarvas M Harwood CR Bron S van Dijl JM Post-translocational folding of secretory proteins in Gram-positive bacteria Biochim Biophys Acta 2004 1694 311 327 15546674
  69. [72]Li H Faury D Morosoli R Impact of amino acid changes in the signal peptide on the secretion of the Tat-dependent xylanase C from Streptomyces lividans FEMS Microbiol Lett 2006 255 268 274 10.1111/j.1574-6968.2005.00081.x 16448505 · DOI
  70. [73]Ulfig A Fröbel J Lausberg F Blümmel AS Heide AK Müller M Freudl R The h-region of twin-arginine signal peptides supports productive binding of bacterial Tat precursor proteins to the TatBC receptor complex J Biol Chem 2017 292 10865 10882 10.1074/jbc.M117.788950 28515319 PMC5491773 · DOI
  71. [74]Sagiya Y Yamagata H Udaka S Direct high-level secretion into the culture medium of tuna growth hormone in biologically active form by Bacillus brevis Appl Microbiol Biotechnol 1994 42 358 363 7765778
  72. [75]Takimura Y Kato M Ohta T Yamagata H Udaka S Secretion of human interleukin-2 in biologically active form by Bacillus brevis directly into culture medium Biosci Biotechnol Biochem 1997 61 1858 1861 10.1271/bbb.61.1858 9404065 · DOI
  73. [76]Zhou Y Liu P Gan Y Sandoval W Katakam AK Reichelt M Rangeli L Reilly D Enhancing full-length antibody production by signal peptide engineering Microb Cell Fact 2016 15 47 10.1186/s12934-016-0445-3 26935575 PMC4776426 · DOI
  74. [77]Ravn P Arnau J Madsen SM Vrang A Israelsen H Optimization of signal peptide SP310 for heterologous protein production in Lactococcus lactis Microbiology (UK) 2003 149 2193 2201 10.1099/mic.0.26299-0 12904559 · DOI
  75. [78]Zanen G Houben EN Meima R Tjalsma H Jongbloed JDH Westers H Oudega B Luirink J van Dijl JM Quax WJ Signal peptide hydrophobicity is critical for early stages in protein export by Bacillus subtilis FEBS J 2005 272 4617 4630 10.1111/j.1742-4658.2005.04777.x 16156784 · DOI
  76. [79]Guan C Cui W He X Hu X Xu J Du G Chen J Zhou Z Construction and development of a novel expression system of Streptomyces Protein Expr Purif 2015 113 17 22 10.1016/j.pep.2015.04.009 25956536 · DOI
  77. [80]Mhiri S Mezghani M Mellouli L Ben Ali M Belguith K Bejar S Efficient synthetic signal peptides for Streptomyces Biotechnol Lett 2000 22 1305 1310 10.1023/A:1005678311475 · DOI
  78. [81]Rohe P Venkanna D Kleine B Freudl R Oldiges M An automated workflow for enhancing microbial bioprocess optimization on a novel microbioreactor platform Microb Cell Fact 2012 11 144 10.1186/1475-2859-11-144 23113930 PMC3526558 · DOI

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Authors
Freudl, R.
Affiliations
Forschungszentrum Jülich (DE)
Corresponding author
Freudl, Roland
ORCID
Freudl, Roland
Venue
Microbial Cell Factories
Publisher
Springer Science and Business Media LLC
Published
2018-03-29
Volume
17
Issue
1
Pages
52-52
ISSN
1475-2859 (ISSN-L)
DOI
10.1186/s12934-018-0901-3
PMC
PMC5875014
OpenAlex
W2802730096
Cited by
312
References
3
Citations by year
2026: 31 · 2025: 39 · 2024: 50 · 2023: 39 · 2022: 44 · 2021: 50 · 2020: 32 · 2019: 18 · 2018: 9
FWCI
3.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Microbial Cell Factories (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • JuSER (Forschungszentrum Jülich) (submittedVersion, cc-by)
Funders
Bio.NRW (w0805wb003c)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
Keywords
signal peptide, recombinant protein secretion, prokaryotic expression, Sec pathway, twin-arginine translocation, Tat pathway, protein export, site-directed mutagenesis, random mutagenesis, protein folding, protein stability
MeSH terms
Twin-Arginine-Translocation System, SEC Translocation Channels, Bacterial Proteins, Escherichia coli, Gram-Positive Bacteria, Industrial Microbiology, Recombinant Proteins, Protein Transport, Protein Sorting Signals, Membrane Transport Proteins, Escherichia coli Proteins, Bacterial Secretion Systems

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