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Cited by 14Bacterial biofilms and quorum sensingBacterial Genetics and BiotechnologyMicrobial Metabolic Engineering and Bioproduction

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Modeling the time course of ComX: towards molecular process control for Bacillus wild-type cultivations

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Treinen, Chantal, Magosch, Olivia, Hoffmann, Mareen, Klausmann, Peter, Würtz, Berit, Pfannstiel, Jens, Morabbi Heravi, Kambiz, Lilge, Lars, Hausmann, Rudolf, Henkel, Marius·2021·AMB Express
DOI 10.1186/s13568-021-01306-5PMC PMC8556439
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Abstract

Wild-type cultivations are of invaluable relevance for industrial biotechnology when it comes to the agricultural or food sector. Here, genetic engineering is hardly applicable due to legal barriers and consumer’s demand for GMO-free products. An important pillar for wild-type cultivations displays the genus Bacillus. One of the challenges for Bacillus cultivations is the global ComX-dependent quorum sensing system. Here, molecular process control can serve as a tool to optimize the production process without genetic engineering. To realize this approach, quantitative knowledge of the mechanism is essential, which, however, is often available only to a limited extent. The presented work provides a case study based on the production of cyclic lipopeptide surfactin, whose expression is in dependence of ComX, using natural producer B. subtilis DSM 10 T. First, a surfactin reference process with 40 g/L of glucose was performed as batch fermentation in a pilot scale bioreactor system to gain novel insights into kinetic behavior of ComX in relation to surfactin production. Interestingly, the specific surfactin productivity did not increase linearly with ComX activity. The data were then used to derive a mathematic model for the time course of ComX in dependence of existing biomass, biomass growth as well as a putative ComX-specific protease. The newly adapted model was validated and transferred to other batch fermentations, employing 20 and 60 g/L glucose. The applied approach can serve as a model system for molecular process control strategies, which can thus be extended to other quorum sensing dependent wild-type cultivations.

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  • NRPS gene expression is controlled by cell differentiation processes and in particular by the ComX-mediated quorum sensing mechanism, which enables biomass-related surfactin production.

    “NRPS gene expression is controlled by cell differentiation processes and in particular by the ComX-mediated quorum sensing mechanism, which enables biomass-related surfactin production [4–6].”

    From The influence of growth rate-controlling feeding strategy on the surfactin production in Bacillus subtilis bioreactor processes (2024) · cites this paper as [6]

    The Introduction (page unavailable) describes ComX-mediated quorum sensing activating the surfactin promoter PsrfA and links quorum sensing to cell density. The Discussion (page unavailable) names cell differentiation as another factor that can influence surfactin production, but does not establish that differentiation controls NRPS gene expression specifically. (LLM, conf=0.84)

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References 56 · Cited by 14

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  1. Bacon Schneider K, Palmer TM, Grossman AD (2002) Characterization of comQ and comX, two genes required for production of ComX pheromone in Bacillus subtilis. J Bacteriol 184:410–419 · DOI
  2. Banat IM, Franzetti A, Gandolfi I, Bestetti G, Martinotti MG, Fracchia L, Smyth TJ, Marchant R (2010) Microbial biosurfactants production, applications and future potential. Appl Microbiol Biotechnol 87:427–444 · DOI
  3. Bassler BL (1999) How bacteria talk to each other: regulation of gene expression by quorum sensing. Curr Opin Microbiol 2:582–587 · DOI
  4. Baur C, Krewinkel M, Kutzli I, Kranz B, von Neubeck M, Huptas C, Wenning M, Scherer S, Stoeckel M, Hinrichs J, Stressler T, Fischer L (2015) Isolation and characterisation of a heat-resistant peptidase from Pseudomonas panacis withstanding general UHT processes. Int Dairy J 49:46–55 · DOI
  5. Bertani G (1951) Studies on lysogenesis. I. The mode of phage liberation by lysogenic Escherichia coli. J Bacteriol 62:293–300 · DOI
  6. Charney J, Tomarelli RM (1947) A colorimetric method for the determination of the proteolytic activity of duodenal juice. J Biol Chem 171:501–505 · DOI
  7. Comella N, Grossman AD (2005) Conservation of genes and processes controlled by the quorum response in bacteria: characterization of genes controlled by the quorum-sensing transcription factor ComA in Bacillus subtilis. Mol Microbiol 57:1159–1174 · DOI
  8. Cooper DG, Macdonald CR, Duff SJB, Kosaric N (1981) Enhanced production of surfactin from Bacillus subtilis by continuous product removal and metal cation additions. Appl Environ Microbiol 42:408–412 · DOI · Paper page
  9. Cosby WM, Vollenbroich D, Lee OH, Zuber P (1998) Altered srf expression in Bacillus subtilis resulting from changes in culture pH is dependent on the Spo0K oligopeptide permease and the ComQX system of extracellular control. J Bacteriol 180:1438–1445 · DOI
  10. de Araujo LV, Guimarães CR, da Silva Marquita RL, Santiago VM, de Souza MP, Nitschke M, Freire DMG (2016) Rhamnolipid and surfactin: anti-adhesion/antibiofilm and antimicrobial effects. Food Control 63:171–178 · DOI
  11. Deleu M, Razafindralambo H, Popineua Y, Jacques P, Thonart P, Paquot M (1999) Interfacial and emulsifying properties of lipopeptides from Bacillus subtilis. Colloids Surf A Physicochem Eng Asp 152:3–10 · DOI
  12. Dogsa I, Spacapan M, Dragoš A, Danevčič T, Pandur Ž, Mandic-Mulec I (2021) Peptide signaling without feedback in signal production operates as a true quorum sensing communication system in Bacillus subtilis. Commun Biol 4:58 · DOI
  13. Elshaghabee FMF, Rokana N, Gulhane RD, Sharma C, Panwar H (2017) Bacillus as potential probiotics: status, concerns, and future perspectives. Front Microbiol 8:1490 · DOI
  14. Geissler M, Oellig C, Moss K, Schwack W, Henkel M, Hausmann R (2017) High-performance thin-layer chromatography (HPTLC) for the simultaneous quantification of the cyclic lipopeptides surfactin, iturin A and fengycin in culture samples of Bacillus species. J Chromatogr B 1044–1045:214–224 · DOI · Paper page
  15. Geissler M, Kühle I, Morabbi Heravi K, Altenbuchner J, Henkel M, Hausmann R (2019a) Evaluation of surfactin synthesis in a genome reduced Bacillus subtilis strain. AMB Expr 9:84 · DOI · Paper page
  16. Geissler M, Morabbi Heravi K, Henkel M, Hausmann R (2019b) Lipopeptide biosurfactants from Bacillus species. In: Hayes DG, Solaiman DK, Ashby RD (eds) Biobased surfactants, 2nd edn. Elsevier, Amsterdam, pp 205–240 · DOI
  17. Hamoen LW, Venema G, Kuipers OP (2003) Controlling competence in Bacillus subtilis: shared use of regulators. Microbiology 149:9–17 · DOI
  18. Hanlon P, Sewalt V (2021) GEMs: genetically engineered microorganisms and the regulatory oversight of their uses in modern food production. Crit Rev Food Sci Nutr 61:959–970 · DOI
  19. Harwood CR, Cutting SM (eds) (1990) Molecular biological methods for Bacillus. Wiley, Chichester
  20. Harwood CR (1992) Bacillus subtilis and its relatives: molecular biological and industrial workhorses. Trends Biotechnol 10:247–256 · DOI
  21. Henkel M, Schmidberger A, Kühnert C, Beuker J, Bernard T, Schwartz T, Syldatk C, Hausmann R (2013) Kinetic modeling of the time course of N-butyryl-homoserine lactone concentration during batch cultivations of Pseudomonas aeruginosa PAO1. Appl Microbiol Biotechnol 97:7607–7616 · DOI
  22. Hoffmann M, Fernandez Cano Luna DS, Xiao S, Stegemüller L, Rief K, Morabbi Heravi K, Lilge L, Henkel M, Hausmann R (2020) Towards the anaerobic production of surfactin using Bacillus subtilis. Front Bioeng Biotechnol 8:554903 · DOI · Paper page
  23. Hoffmann M, Braig A, Fernandez Cano Luna DS, Rief K, Becker P, Treinen C, Klausmann P, Morabbi Heravi K, Henkel M, Lilge L, Hausmann R (2021a) Evaluation of an oxygen-dependent self-inducible surfactin synthesis in B. subtilis by substitution of native promoter PsrfA by anaerobically active PnarG and PnasD. AMB Expr 11:57 · DOI
  24. Hoffmann M, Mück D, Grossmann L, Greiner L, Klausmann P, Henkel M, Lilge L, Weiss J, Hausmann R (2021b) Surfactin from Bacillus subtilis displays promising characteristics as O/W-emulsifier for food formulations. Colloids Surf B Biointerfaces 203:111749 · DOI
  25. Jacques P (2011) Surfactin and other lipopeptides from Bacillus spp. In: Soberón-Chávez G (ed) Biosurfactants. Microbiology monographs, vol 20. Springer. Berlin, Heidelberg, pp 57–91
  26. Kamino K, Fujimoto K, Sawai S (2011) Collective oscillations in developing cells: insights from simple systems. Dev Growth Differ 53:503–517 · DOI
  27. Koo BM, Kritikos G, Farelli JD, Todor H, Tong K, Kimsey H, Wapinski I, Galardini M, Cabal A, Peters JM, Hachmann A-B, Rudner DZ, Allen KN, Typas A, Gross CA (2017) Construction and analysis of two genome-scale deletion libraries for Bacillus subtilis. Cell Syst 4:291–305 · DOI
  28. Koutinas M, Kiparissides A, Pistikopoulos EN, Mantalaris A (2012) Bioprocess systems engineering: transferring traditional process engineering principles to industrial biotechnology. Comput Struct Biotechnol J 3:e201210022 · DOI
  29. Liu Y, Li J, Du G, Chen J, Liu L (2017) Metabolic engineering of Bacillus subtilis fueled by systems biology: recent advances and future directions. Biotechnol Adv 35:20–30 · DOI
  30. Liu D, Mannan AA, Han Y, Oyarzún DA, Zhang F (2018) Dynamic metabolic control: towards precision engineering of metabolism. J Ind Microbiol Biotechnol 45:535–543 · DOI
  31. Magnuson R, Solomon J, Grossman AD (1994) Biochemical and genetic characterization of a competence pheromone from B. subtilis. Cell 77:207–216 · DOI
  32. Miller JH (1972) Experiments in molecular genetics. Cold Spring Harbor Laboratory Press, Cold Spring Harbor
  33. Nakano MM, Magnuson R, Myers A, Curry J, Grossman AD, Zuber P (1991) srfA is an operon required for surfactin production, competence development, and efficient sporulation in Bacillus subtilis. J Bacteriol 173:1770–1778 · DOI
  34. Naughton PJ, Marchant R, Naughton V, Banat IM (2019) Microbial biosurfactants: current trends and applications in agricultural and biomedical industries. J Appl Microbiol 127:12–28 · DOI
  35. Nitschke M, Costa S (2007) Biosurfactants in food industry. Trends Food Sci Technol 18:252–259 · DOI · Paper page
  36. Okada M, Sato I, Cho SJ, Iwata H, Nishio T, Dubnau D, Sakagami Y (2005) Structure of the Bacillus subtilis quorum-sensing peptide pheromone ComX. Nat Chem Biol 1:23–24 · DOI
  37. Okada M, Yamaguchi H, Sato I, Tsuji F, Qi J, Dubnau D, Sakagami Y (2007) Acid labile ComX pheromone from Bacillus mojavensis RO-H-1. Biosci Biotechnol Biochem 71:1807–1810 · DOI
  38. Ongena M, Jacques P (2008) Bacillus lipopeptides: versatile weapons for plant disease biocontrol. Trends Microbiol 16:115–125 · DOI
  39. Peters HP, Sawicka M (2007) German reactions to genetic engineering in food production. In: Brossard D, Shanahan J, Nesbitt TC (eds) The public, the media and agricultural biotechnology. Cabi, Wallingford (UK), pp 57–96 · DOI
  40. Rajput A, Gupta AK, Kumar M (2015) Prediction and analysis of quorum sensing peptides based on sequence features. PLoS ONE 10:e0120066 · DOI
  41. Rangarajan V, Clarke KG (2015) Process development and intensification for enhanced production of Bacillus lipopeptides. Biotechnol Genet Eng Rev 31:46–68 · DOI
  42. Schallmey M, Singh A, Ward OP (2004) Developments in the use of Bacillus species for industrial production. Can J Microbiol 50:1–17 · DOI
  43. Sewalt V, Shanahan D, Gregg L, La Marta J, Carrillo R (2016) The generally recognized as safe (GRAS) process for industrial microbial enzymes. Ind Biotechnol 12:295–302 · DOI
  44. Shrivastava A, Gupta VB (2011) Methods for the determination of limit of detection and limit of quantitation of the analytical methods. Chron Young Sci 2:21–25 · DOI
  45. Spacapan M, Danevčič T, Mandic-Mulec I (2018) ComX-induced exoproteases degrade ComX in Bacillus subtilis PS-216. Front Microbiol 9:105 · DOI
  46. Su Y, Liu C, Fang H, Zhang D (2020) Bacillus subtilis: a universal cell factory for industry, agriculture, biomaterials and medicine. Microb Cell Fact 19:173 · DOI
  47. Tiwari S, Prasad V, Lata C (2019) Bacillus: plant growth promoting bacteria for sustainable agriculture and environment. In: Singh JS, Singh DP (eds) New and future developments in microbial biotechnology and bioengineering. Elsevier, Amsterdam, pp 43–55 · DOI
  48. van Dijl JM, Hecker M (2013) Bacillus subtilis: from soil bacterium to super-secreting cell factory. Microb Cell Fact 12:3 · DOI
  49. Venayak N, Anesiadis N, Cluett WR, Mahadevan R (2015) Engineering metabolism through dynamic control. Curr Opin Biotechnol 34:142–152 · DOI
  50. Wei Y-H, Chu I-M (1998) Enhancement of surfactin production in iron-enriched media by Bacillus subtilis ATCC 21332. Enzyme Microb Technol 22:724–728 · DOI
  51. Westers L, Westers H, Quax WJ (2004) Bacillus subtilis as cell factory for pharmaceutical proteins: a biotechnological approach to optimize the host organism. Biochim Biophys Acta Mol Cell Res 1694:299–310 · DOI
  52. Willenbacher J, Zwick M, Mohr T, Schmid F, Syldatk C, Hausmann R (2014) Evaluation of different Bacillus strains in respect of their ability to produce surfactin in a model fermentation process with integrated foam fractionation. Appl Microbiol Biotechnol 98:9623–9632 · DOI
  53. Zhao H, Shao D, Jiang C, Shi J, Li Q, Huang Q, Rajoka MSR, Yang H, Jin M (2017) Biological activity of lipopeptides from Bacillus. Appl Microbiol Biotechnol 101:5951–5960 · DOI

Metadata

Authors
Treinen, C., Magosch, O., Hoffmann, M., Klausmann, P., Würtz, B., Pfannstiel, J., Morabbi Heravi, K., Lilge, L., Hausmann, R., & Henkel, M.
Affiliations
University of Hohenheim (DE)
Corresponding author
Henkel, Marius
ORCID
Venue
AMB Express
Publisher
Springer Science and Business Media LLC
Published
2021-10-29
Volume
11
Issue
1
Pages
144-144
ISSN
2191-0855 (ISSN-L)
DOI
10.1186/s13568-021-01306-5
PMC
PMC8556439
OpenAlex
W3210537744
Cited by
14
References
56
Citations by year
2026: 3 · 2025: 2 · 2024: 5 · 2023: 3 · 2022: 1
FWCI
0.78
Type
journal article
Language
en
Open access
Licence
Locations
  • AMB Express (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Universität Hohenheim
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
Keywords
ComX, quorum sensing, Bacillus subtilis, surfactin, mathematical modeling, batch fermentation, glucose concentration

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