Open Access

Bacterial cell factories for recombinant protein production; expanding the catalogue

Microbial Cell Factories201312:113

https://doi.org/10.1186/1475-2859-12-113

Received: 29 October 2013

Accepted: 30 October 2013

Published: 18 November 2013

Escherichia coli has been the pioneering host for recombinant protein production, since the original recombinant DNA procedures were developed using its genetic material and infecting bacteriophages. As a consequence, and because of the accumulated know-how on E. coli genetics and physiology and the increasing number of tools for genetic engineering adapted to this bacterium, E. coli is the preferred host when attempting the production of a new protein. Also, it is still the first choice for protein production at laboratory and industrial scales for an important number of proteins, being fast growth and simple culture procedures critical issues. When searching for an ideal system for protein production, this bacterial species is clearly far from offering, in generic terms, optimal conditions for protein production and downstream. Plasmid loss and antibiotic-based maintenance, undesired chemical inducers of gene expression, plasmid/protein-mediated metabolic burden and stress responses, lack of post-translational modifications (including the inability to form disulphide bonds), none or poor secretion, protein aggregation and proteolytic digestion, endotoxin contamination and complex downstream are among the main obstacles encountered during protein production in E. coli. In the pharmaceutical scenario, proper protein glycosylation is often requested and simplest purification procedures become highly desirable when pursuing cost-effective bioproduction. In this context, the yeast Sacharomyces cerevisae, diverse mammalian cell lines, insect cells and whole plant and animals (as transgenic systems) are being incorporated to the protein production scenario [1], and many of these products have been already approved for use as protein drugs [2]. Other (less conventional) yeast species and a more limited number of species of filamentous fungi [3], molds [4], moss [5], algae [6] and protozoa [7] are also under development as potential suppliers of recombinant proteins. The engineering of such systems could represent a promising way to the cost effective production of high quality protein versions that biotechnology and biomedical industries are steadily demanding. The potential and versatility of these platforms as protein producers or in general, as cell factories for added value products such as chemicals, amino acids or vitamins has been stressed in recent experimental reports or reviews [817]. Despite this, it must be noted that adapting large-scale production processes to the biological complexity of some of these systems might represent, in some cases, an unaffordable task.

From a different angle, bacterial hosts others than E. coli are attracting attention as cell factories due to their metabolic diversity and biosynthetic potential derived from adaptation to extremely diverse environments. The most important bacterial groups explored as cell factories for recombinant proteins and their associated potentialities are summarized in Table 1. The implementation of lactic acid bacteria as a routine cell factory expands their applications from conventional food microbiology [1821] to protein production and also protein drug display and delivery [2229], taking advantage of the generically recognized as safe (GRAS) features of this platform. Improved solubility in halophillic and cold-adapted bacteria, enhanced secretion in acid lactic bacteria and in general in endotoxin-free gram-positive species and post-translational modifications in mycobacteria among others are highly appealing properties in protein production, that can be of special value for specific difficult-to-express proteins. While exhibiting most of the above mentioned limitations linked to prokaryotic-based production, exploring bacterial species other than E. coli should be not abandoned but fully supported as it will not only expand the current catalogue of cell factories but also offer novel process opportunities in easily cultivable/scalable systems that might pose, in generic terms, less methodological issues than unconventional protein production systems [30].
Table 1

The most important bacterial groups explored as cell factories for recombinant protein production

 

Host

Main features

Reviewsa

Main bacterial Species

Case proteins

References

Proteobacteria

Caulobacteria

Easy purification of secreted RSaA fusions

[31, 32]

Caulobacter crescentus

Hematopoietic necrosis virus capsid proteins

[33]

    

β-1,4-glycanase

[34]

Phototrophic bacteria

High production of membrane proteins

[35]

Rodhobacter sphaeroides

Membrane proteins

[35]

Cold adapted bacteria

Improved protein folding

[36, 37]

Pseudoalteromonas haloplanktis

3H6 Fab

[38]

    

Human nerve growth factor

[39]

   

Shewanella sp. strain Ac10

β-Lactamase, peptidases, glucosidase

[40]

Pseudomonads

Efficient secretion

[41]

Pseudomonas fluorescens

Human granulocyte colony-stimulating factor

[42]

   

Pseudomonas putida

Single chain Fv fragments

[43]

   

Pseudomonas aeruginosa

Penicillin G acylase

[44]

Halophilic bacteria

Solubility favored

[45]

Halomonas elongata

β-Lactamase

[45]

   

Chromohalobacter salexigens

Nucleoside diphosphate kinase

[46]

Actinobacteria

Streptomycetes

Efficient secretion

[47, 48]

Streptomyces lividans

M. tuberculosis antigens

[49]

   

Streptomyces griseus

Trypsin

[50]

Nocardia

Efficient secretion

[48]

Nocardia lactamdurans

Lysine-6-aminotransferase

[51]

Mycobacteria

Posttranslational modifications

[52]

Mycobacterium smegmatis

Hsp65-hIL-2 fusion protein

[53]

    

Mycobacterial proteins

[54]

Coryneform bacteria

High-level production and secretion; GRAS

[48, 55]

Corynebacterium glutamicum

Protein-glutaminase

[56]

   

Corynebacterium ammoniagenes

Pro-transglutaminase

[57]

   

Brevibacterium lactofermentum

Cellulases

[58]

Firmicutes

Bacilli

High-level production and secretion

[5964]

Bacillus subtilis

β-Galactosidase

[65]

   

Bacillus brevis

Disulfide isomerase

[66, 67]

   

Bacillus megaterium

Antibodies

[68]

   

Bacillus licheniformis

Subtilisin

[69]

   

Bacillus amyloliquefaciens

Amylases

[70]

Lactic acid bacteria

Secretion; GRAS

[2224, 71]

Lactococcus lactis

Fibronectin-binding protein A, internalin A, GroEL

[72, 73]

   

Lactobacillus plantarum

β-Galactosidase

[74]

   

Lactobacillus casei

VP2-VP3 fusion protein of infectious pancreatic necrosis virus

[75]

   

Lactobacillus reuteri

Pediocin PA-1

[76]

   

Lactobacillus gasseri

CC chemokines

[77]

a Generic reviews about the biological platform or about specific tools for protein production.

Towards a progressively more competitive biological synthesis by microbes [78] and assisted by expanding systems metabolic engineering and synthetic biology tools [79], industrial biotechnology should desirably find within the prokaryotic world, a growing spectrum of alternatives to eukaryotic cell factories, that apart from easy and cost-effective cultivation provide unexpectedly high metabolic versatility and biosafety of their protein-based products. In some cases and at a large extent, it is solving some of the main issues posed by E. coli as traditional producer or recombinant proteins.

Declarations

Acknowledgments

We are indebted to MINECO (BFU2010-17450), AGAUR (2009SGR-0108) and CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN, Spain) for funding our research on protein-based therapeutics and the Protein Production Platform (PPP). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 20082011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. AV received an ICREA ACADEMIA award.

Authors’ Affiliations

(1)
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona
(2)
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN)
(3)
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona

References

  1. Sorensen HP: Towards universal systems for recombinant gene expression. Microb Cell Fact. 2010, 9: 27-10.1186/1475-2859-9-27.View ArticleGoogle Scholar
  2. Ferrer-Miralles N, Domingo-Espin J, Corchero JL, Vazquez E, Villaverde A: Microbial factories for recombinant pharmaceuticals. Microb Cell Fact. 2009, 8: 17-10.1186/1475-2859-8-17.View ArticleGoogle Scholar
  3. Ward OP: Production of recombinant proteins by filamentous fungi. Biotechnol Adv. 2012, 30: 1119-1139. 10.1016/j.biotechadv.2011.09.012.View ArticleGoogle Scholar
  4. Arya R, Bhattacharya A, Saini KS: Dictyostelium discoideum –a promising expression system for the production of eukaryotic proteins. FASEB J. 2008, 22: 4055-4066. 10.1096/fj.08-110544.View ArticleGoogle Scholar
  5. Decker EL, Reski R: Moss bioreactors producing improved biopharmaceuticals. Curr Opin Biotechnol. 2007, 18: 393-398. 10.1016/j.copbio.2007.07.012.View ArticleGoogle Scholar
  6. Potvin G, Zhang Z: Strategies for high-level recombinant protein expression in transgenic microalgae: a review. Biotechnol Adv. 2010, 28: 910-918.View ArticleGoogle Scholar
  7. LEXSY Biosafety Status. 2013, http://www.jenabioscience.com/cms/en/1/browse/1879_biosafety.html . 2013 Ref Type: Electronic Citation
  8. Porro D, Gasser B, Fossati T, Maurer M, Branduardi P, Sauer M, et al: Production of recombinant proteins and metabolites in yeasts: when are these systems better than bacterial production systems?. Appl Microbiol Biotechnol. 2011, 89: 939-948. 10.1007/s00253-010-3019-z.View ArticleGoogle Scholar
  9. Corchero JL, Gasser B, Resina D, Smith W, Parrilli E, Vazquez F, et al: Unconventional microbial systems for the cost-efficient production of high-quality protein therapeutics. Biotechnol Adv. 2013, 31: 140-153. 10.1016/j.biotechadv.2012.09.001.View ArticleGoogle Scholar
  10. Mustalahti E, Saloheimo M, Joensuu JJ: Intracellular protein production in Trichoderma reesei (Hypocrea jecorina) with hydrophobin fusion technology. N Biotechnol. 2011, 30: 262-268.View ArticleGoogle Scholar
  11. Idiris A, Tohda H, Kumagai H, Takegawa K: Engineering of protein secretion in yeast: strategies and impact on protein production. Appl Microbiol Biotechnol. 2010, 86: 403-417. 10.1007/s00253-010-2447-0.View ArticleGoogle Scholar
  12. Decker EL, Reski R: Current achievements in the production of complex biopharmaceuticals with moss bioreactors. Bioprocess Biosyst Eng. 2008, 31: 3-9. 10.1007/s00449-007-0151-y.View ArticleGoogle Scholar
  13. Gerngross TU: Advances in the production of human therapeutic proteins in yeasts and filamentous fungi. Nat Biotechnol. 2004, 22: 1409-1414. 10.1038/nbt1028.View ArticleGoogle Scholar
  14. Spolaore P, Joannis-Cassan C, Duran E, Isambert A: Commercial applications of microalgae. J Biosci Bioeng. 2006, 101: 87-96. 10.1263/jbb.101.87.View ArticleGoogle Scholar
  15. Rme-Vega TC, Lim DK, Timmins M, Vernen F, Li Y, Schenk PM: Microalgal biofactories: a promising approach towards sustainable omega-3 fatty acid production. Microb Cell Fact. 2012, 11: 96-10.1186/1475-2859-11-96.View ArticleGoogle Scholar
  16. Hempel F, Bozarth AS, Lindenkamp N, Klingl A, Zauner S, Linne U, et al: Microalgae as bioreactors for bioplastic production. Microb Cell Fact. 2011, 10: 81-10.1186/1475-2859-10-81.View ArticleGoogle Scholar
  17. Specht E, Miyake-Stoner S, Mayfield S: Micro-algae come of age as a platform for recombinant protein production. Biotechnol Lett. 2010, 32: 1373-1383. 10.1007/s10529-010-0326-5.View ArticleGoogle Scholar
  18. Rhee SJ, Lee JE, Lee CH: Importance of lactic acid bacteria in Asian fermented foods. Microb Cell Fact. 2011, 10 (1): S5-10.1186/1475-2859-10-5.View ArticleGoogle Scholar
  19. De Vos WM: Systems solutions by lactic acid bacteria: from paradigms to practice. Microb Cell Fact. 2011, 10 (1): S2-10.1186/1475-2859-10-2.View ArticleGoogle Scholar
  20. Arendt EK, Moroni A, Zannini E: Medical nutrition therapy: use of sourdough lactic acid bacteria as a cell factory for delivering functional biomolecules and food ingredients in gluten free bread. Microb Cell Fact. 2011, 10 (1): S15-10.1186/1475-2859-10-15.View ArticleGoogle Scholar
  21. Teusink B, Bachmann H, Molenaar D: Systems biology of lactic acid bacteria: a critical review. Microb Cell Fact. 2011, 10 (1): S11-10.1186/1475-2859-10-11.View ArticleGoogle Scholar
  22. Garcia-Fruitos E: Lactic Acid Bacteria: a promising alternative for recombinant protein production. Microb Cell Fact. 2012, 11: 157-10.1186/1475-2859-11-157.View ArticleGoogle Scholar
  23. Peterbauer C, Maischberger T, Haltrich D: Food-grade gene expression in lactic acid bacteria. Biotechnol J. 2011, 6: 1147-1161. 10.1002/biot.201100034.View ArticleGoogle Scholar
  24. Morello E, Bermudez-Humaran LG, Llull D, Sole V, Miraglio N, Langella P, et al: Lactococcus lactis, an efficient cell factory for recombinant protein production and secretion. J Mol Microbiol Biotechnol. 2008, 14: 48-58. 10.1159/000106082.View ArticleGoogle Scholar
  25. Pontes DS, de Azevedo MS, Chatel JM, Langella P, Azevedo V, Miyoshi A: Lactococcus lactis as a live vector: heterologous protein production and DNA delivery systems. Protein Expr Purif. 2011, 79: 165-175. 10.1016/j.pep.2011.06.005.View ArticleGoogle Scholar
  26. Daniel C, Roussel Y, Kleerebezem M, Pot B: Recombinant lactic acid bacteria as mucosal biotherapeutic agents. Trends Biotechnol. 2011, 29: 499-508. 10.1016/j.tibtech.2011.05.002.View ArticleGoogle Scholar
  27. Hu S, Kong J, Sun Z, Han L, Kong W, Yang P: Heterologous protein display on the cell surface of lactic acid bacteria mediated by the S-layer protein. Microb Cell Fact. 2011, 10: 86-10.1186/1475-2859-10-86.View ArticleGoogle Scholar
  28. Bermudez-Humaran LG, Kharrat P, Chatel JM, Langella P: Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Microb Cell Fact. 2011, 10 (1): S4-10.1186/1475-2859-10-4.View ArticleGoogle Scholar
  29. Scavone P, Miyoshi A, Rial A, Chabalgoity A, Langella P, Azevedo V, et al: Intranasal immunisation with recombinant lactococcus lactis displaying either anchored or secreted forms of proteus mirabilis MrpA fimbrial protein confers specific immune response and induces a significant reduction of kidney bacterial colonisation in mice. Microbes Infect. 2007, 9: 821-828. 10.1016/j.micinf.2007.02.023.View ArticleGoogle Scholar
  30. Chen R: Bacterial expression systems for recombinant protein production: E. coli and beyond. Biotechnol Adv. 2012, 30: 1102-1107. 10.1016/j.biotechadv.2011.09.013.View ArticleGoogle Scholar
  31. Terpe K: Overview of tag protein fusions: from molecular and biochemical fundamentals to commercial systems. Appl Microbiol Biotechnol. 2003, 60: 523-533.View ArticleGoogle Scholar
  32. Hahn HP, von Specht BU: Secretory delivery of recombinant proteins in attenuated salmonella strains: potential and limitations of type I protein transporters. FEMS Immunol Med Microbiol. 2003, 37: 87-98. 10.1016/S0928-8244(03)00092-0.View ArticleGoogle Scholar
  33. Simon B, Nomellini J, Chiou P, Bingle W, Thornton J, Smit J, et al: Recombinant vaccines against infectious hematopoietic necrosis virus: production by the Caulobacter crescentus S-layer protein secretion system and evaluation in laboratory trials. Dis Aquat Organ. 2001, 44: 17-27.View ArticleGoogle Scholar
  34. Duncan G, Tarling CA, Bingle WH, Nomellini JF, Yamage M, Dorocicz IR, et al: Evaluation of a new system for developing particulate enzymes based on the surface (S)-layer protein (RsaA) of Caulobacter crescentus: fusion with the beta-1,4-glycanase (Cex) from the cellulolytic bacterium Cellulomonas fimi yields a robust, catalytically active product. Appl Biochem Biotechnol. 2005, 127: 95-110. 10.1385/ABAB:127:2:095.View ArticleGoogle Scholar
  35. Laible PD, Scott HN, Henry L, Hanson DK: Towards higher-throughput membrane protein production for structural genomics initiatives. J Struct Funct Genomics. 2004, 5: 167-172.View ArticleGoogle Scholar
  36. Duilio A, Tutino ML, Marino G: Recombinant protein production in Antarctic Gram-negative bacteria. Methods Mol Biol. 2004, 267: 225-237.Google Scholar
  37. Rippa V, Papa R, Giuliani M, Pezzella C, Parrilli E, Tutino ML, et al: Regulated recombinant protein production in the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125. Methods Mol Biol. 2012, 824: 203-218. 10.1007/978-1-61779-433-9_10.View ArticleGoogle Scholar
  38. Giuliani M, Parrilli E, Ferrer P, Baumann K, Marino C, Tutino ML: Process optimization for recombinant protein production in the psychrophilic bacterium Pseudoalteromonas haloplanktis. Process Biochem. 2011, 46: 953-959. 10.1016/j.procbio.2011.01.011.View ArticleGoogle Scholar
  39. Vigentini I, Merico A, Tutino ML, Compagno C, Marino G: Optimization of recombinant human nerve growth factor production in the psychrophilic Pseudoalteromonas haloplanktis. J Biotechnol. 2006, 127: 141-150. 10.1016/j.jbiotec.2006.05.019.View ArticleGoogle Scholar
  40. Miyake R, Kawamoto J, Wei YL, Kitagawa M, Kato I, Kurihara T, et al: Construction of a low-temperature protein expression system using a cold-adapted bacterium, Shewanella sp. strain Ac10, as the host. Appl Environ Microbiol. 2007, 73: 4849-4856. 10.1128/AEM.00824-07.View ArticleGoogle Scholar
  41. Retallack DM, Jin H, Chew L: Reliable protein production in a Pseudomonas fluorescens expression system. Protein Expr Purif. 2011, 81: 157-165.View ArticleGoogle Scholar
  42. Jin H, Cantin GT, Maki S, Chew LC, Resnick SM, Ngai J, et al: Soluble periplasmic production of human granulocyte colony-stimulating factor (G-CSF) in Pseudomonas fluorescens. Protein Expr Purif. 2011, 78: 69-77. 10.1016/j.pep.2011.03.002.View ArticleGoogle Scholar
  43. Dammeyer T, Steinwand M, Kruger SC, Dubel S, Hust M, Timmis KN: Efficient production of soluble recombinant single chain Fv fragments by a Pseudomonas putida strain KT2440 cell factory. Microb Cell Fact. 2011, 10: 11-10.1186/1475-2859-10-11.View ArticleGoogle Scholar
  44. Krzeslak J, Braun P, Voulhoux R, Cool RH, Quax WJ: Heterologous production of Escherichia coli penicillin G acylase in Pseudomonas aeruginosa. J Biotechnol. 2009, 142: 250-258. 10.1016/j.jbiotec.2009.05.005.View ArticleGoogle Scholar
  45. Tokunaga H, Arakawa T, Tokunaga M: Novel soluble expression technologies derived from unique properties of halophilic proteins. Appl Microbiol Biotechnol. 2010, 88: 1223-1231. 10.1007/s00253-010-2832-8.View ArticleGoogle Scholar
  46. Nagayoshi C, Tokunaga H, Hayashi A, Harazono H, Hamasaki K, Ando A, et al: Efficient expression of haloarchaeal nucleoside diphosphate kinase via strong porin promoter in moderately halophilic bacteria. Protein Pept Lett. 2006, 13: 611-615. 10.2174/092986606777145760.View ArticleGoogle Scholar
  47. Anne J, Maldonado B, Van IJ, Van ML, Bernaerts K: Recombinant protein production and streptomycetes. J Biotechnol. 2012, 158: 159-167. 10.1016/j.jbiotec.2011.06.028.View ArticleGoogle Scholar
  48. Liu L, Yang H, Shin HD, Li J, Du G, Chen J: Recent advances in recombinant protein expression by Corynebacterium, Brevibacterium, and Streptomyces: from transcription and translation regulation to secretion pathway selection. Appl Microbiol Biotechnol. 2013, 97: 9597-9608. 10.1007/s00253-013-5250-x.View ArticleGoogle Scholar
  49. Ayala JC, Pimienta E, Rodriguez C, Anne J, Vallin C, Milanes MT, et al: Use of Strep-tag II for rapid detection and purification of Mycobacterium tuberculosis recombinant antigens secreted by Streptomyces lividans. J Microbiol Methods. 2013, 94: 192-198. 10.1016/j.mimet.2013.06.004.View ArticleGoogle Scholar
  50. Chi WJ, Song JH, Oh EA, Park SW, Chang YK, Kim ES, et al: Medium optimization and application of an affinity column chromatography for streptomyces griseus trypsin production from the recombinant Streptomyces griseus. J Microbiol Biotechnol. 2009, 19: 1191-1196.View ArticleGoogle Scholar
  51. Chary VK, de la Fuente JL, Leitao AL, Liras P, Martin JF: Overexpression of the lat gene in Nocardia lactamdurans from strong heterologous promoters results in very high levels of lysine-6-aminotransferase and up to two-fold increase in cephamycin C production. Appl Microbiol Biotechnol. 2000, 53: 282-288. 10.1007/s002530050022.View ArticleGoogle Scholar
  52. Connell ND: Expression systems for use in actinomycetes and related organisms. Curr Opin Biotechnol. 2001, 12: 446-449. 10.1016/S0958-1669(00)00243-3.View ArticleGoogle Scholar
  53. Guo XQ, Wei YM, Yu B: Recombinant Mycobacterium smegmatis expressing Hsp65-hIL-2 fusion protein and its influence on lymphocyte function in mice. Asian Pac J Trop Med. 2012, 5: 347-351. 10.1016/S1995-7645(12)60056-X.View ArticleGoogle Scholar
  54. Noens EE, Williams C, Anandhakrishnan M, Poulsen C, Ehebauer MT, Wilmanns M: Improved mycobacterial protein production using a Mycobacterium smegmatis groEL1DeltaC expression strain. BMC Biotechnol. 2011, 11: 27-10.1186/1472-6750-11-27.View ArticleGoogle Scholar
  55. Srivastava P, Deb JK: Gene expression systems in corynebacteria. Protein Expr Purif. 2005, 40: 221-229. 10.1016/j.pep.2004.06.017.View ArticleGoogle Scholar
  56. Kikuchi Y, Itaya H, Date M, Matsui K, Wu LF: Production of Chryseobacterium proteolyticum protein-glutaminase using the twin-arginine translocation pathway in Corynebacterium glutamicum. Appl Microbiol Biotechnol. 2008, 78: 67-74. 10.1007/s00253-007-1283-3.View ArticleGoogle Scholar
  57. Itaya H, Kikuchi Y: Secretion of Streptomyces mobaraensis pro-transglutaminase by coryneform bacteria. Appl Microbiol Biotechnol. 2008, 78: 621-625. 10.1007/s00253-007-1340-y.View ArticleGoogle Scholar
  58. Paradis FW, Warren RA, Kilburn DG, Miller RC: The expression of Cellulomonas fimi cellulase genes in Brevibacterium lactofermentum. Gene. 1987, 61: 199-206. 10.1016/0378-1119(87)90114-4.View ArticleGoogle Scholar
  59. 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.View ArticleGoogle Scholar
  60. 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.View ArticleGoogle Scholar
  61. Westers L, Westers H, Quax WJ: Bacillus subtilis as cell factory for pharmaceutical proteins: a biotechnological approach to optimize the host organism. Biochim Biophys Acta. 2004, 1694: 299-310. 10.1016/j.bbamcr.2004.02.011.View ArticleGoogle Scholar
  62. Pohl S, Harwood CR: Heterologous protein secretion by bacillus species from the cradle to the grave. Adv Appl Microbiol. 2010, 73: 1-25.View ArticleGoogle Scholar
  63. Biedendieck R, Bunk B, Furch T, Franco-Lara E, Jahn M, Jahn D: Systems biology of recombinant protein production in bacillus megaterium. Adv Biochem Eng Biotechnol. 2010, 120: 133-161.Google Scholar
  64. Schallmey M, Singh A, Ward OP: Developments in the use of Bacillus species for industrial production. Can J Microbiol. 2004, 50: 1-17. 10.1139/w03-076.View ArticleGoogle Scholar
  65. Yang M, Zhang W, Ji S, Cao P, Chen Y, Zhao X: Generation of an artificial double promoter for protein expression in Bacillus subtilis through a promoter trap system. PLoS One. 2013, 8: e56321-10.1371/journal.pone.0056321.View ArticleGoogle Scholar
  66. Kajino T, Ohto C, Muramatsu M, Obata S, Udaka S, Yamada Y, et al: A protein disulfide isomerase gene fusion expression system that increases the extracellular productivity of Bacillus brevis. Appl Environ Microbiol. 2000, 66: 638-642. 10.1128/AEM.66.2.638-642.2000.View ArticleGoogle Scholar
  67. Kajino T, Kato K, Miyazaki C, Asami O, Hirai M, Yamada Y, et al: Isolation of a protease-deficient mutant of Bacillus brevis and efficient secretion of a fungal protein disulfide isomerase by the mutant. J Biosci Bioeng. 1999, 87: 37-42. 10.1016/S1389-1723(99)80005-X.View ArticleGoogle Scholar
  68. David F, Steinwand M, Hust M, Bohle K, Ross A, Dubel S, et al: Antibody production in Bacillus megaterium: strategies and physiological implications of scaling from micro titer plates to industrial bioreactors. Biotechnol J. 2011, 6: 1516-1531. 10.1002/biot.201000417.View ArticleGoogle Scholar
  69. Toyokawa Y, Takahara H, Reungsang A, Fukuta M, Hachimine Y, Tachibana S, et al: Purification and characterization of a halotolerant serine proteinase from thermotolerant Bacillus licheniformis RKK-04 isolated from Thai fish sauce. Appl Microbiol Biotechnol. 2010, 86: 1867-1875. 10.1007/s00253-009-2434-5.View ArticleGoogle Scholar
  70. Deb P, Talukdar SA, Mohsina K, Sarker PK, Sayem SA: Production and partial characterization of extracellular amylase enzyme from P-001. Springerplus. 2013, 2: 154-10.1186/2193-1801-2-154.View ArticleGoogle Scholar
  71. Le LY, Azevedo V, Oliveira SC, Freitas DA, Miyoshi A, Bermudez-Humaran LG, et al: Protein secretion in Lactococcus lactis: an efficient way to increase the overall heterologous protein production. Microb Cell Fact. 2005, 4: 2-10.1186/1475-2859-4-2.View ArticleGoogle Scholar
  72. Innocentin S, Guimaraes V, Miyoshi A, Azevedo V, Langella P, Chatel JM, et al: Lactococcus lactis expressing either Staphylococcus aureus fibronectin-binding protein A or Listeria monocytogenes internalin A can efficiently internalize and deliver DNA in human epithelial cells. Appl Environ Microbiol. 2009, 75: 4870-4878. 10.1128/AEM.00825-09.View ArticleGoogle Scholar
  73. Miyoshi A, Bermudez-Humaran LG, Ribeiro LA, Le LY, Oliveira SC, Langella P, et al: Heterologous expression of Brucella abortus GroEL heat-shock protein in Lactococcus lactis. Microb Cell Fact. 2006, 5: 14-10.1186/1475-2859-5-14.View ArticleGoogle Scholar
  74. Nguyen TT, Nguyen HA, Arreola SL, Mlynek G, Djinovic-Carugo K, Mathiesen G, et al: Homodimeric beta-galactosidase from Lactobacillus delbrueckii subsp. bulgaricus DSM 20081: expression in Lactobacillus plantarum and biochemical characterization. J Agric Food Chem. 2012, 60: 1713-1721. 10.1021/jf203909e.View ArticleGoogle Scholar
  75. Zhao LL, Liu M, Ge JW, Qiao XY, Li YJ, Liu DQ: Expression of infectious pancreatic necrosis virus (IPNV) VP2-VP3 fusion protein in Lactobacillus casei and immunogenicity in rainbow trouts. Vaccine. 2012, 30: 1823-1829. 10.1016/j.vaccine.2011.12.132.View ArticleGoogle Scholar
  76. Eom JE, Moon SK, Moon GS: Heterologous production of pediocin PA-1 in Lactobacillus reuteri. J Microbiol Biotechnol. 2010, 20: 1215-1218. 10.4014/jmb.1003.03026.View ArticleGoogle Scholar
  77. Damelin LH, Mavri-Damelin D, Klaenhammer TR, Tiemessen CT: Plasmid transduction using bacteriophage Phi(adh) for expression of CC chemokines by Lactobacillus gasseri ADH. Appl Environ Microbiol. 2010, 76: 3878-3885. 10.1128/AEM.00139-10.View ArticleGoogle Scholar
  78. Chen GQ: New challenges and opportunities for industrial biotechnology. Microb Cell Fact. 2012, 11: 111-10.1186/1475-2859-11-111.View ArticleGoogle Scholar
  79. Lee SY, Mattanovich D, Villaverde A: Systems metabolic engineering, industrial biotechnology and microbial cell factories. Microb Cell Fact. 2012, 11: 156-10.1186/1475-2859-11-156.View ArticleGoogle Scholar

Copyright

© Ferrer-Miralles and Villaverde; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement