Skip to main content
Log in

Bioactivity profiling of the extremolyte ectoine as a promising protectant and its heterologous production

  • Review Article
  • Published:
3 Biotech Aims and scope Submit manuscript

Abstract

Ectoine is a compatible solutes that is diffusely dispersed in bacteria and archaea. It plays a significant role as protectant against various external pressures, such as high temperature, high osmolarity, dryness and radiation, in cells. Ectoine can be utilized in cosmetics due to its properties of moisturizing and antiultraviolet. It can also be used in the pharmaceutical industry for treating various diseases. Therefore, strong protection of ectoine creates a high commercial value. Its current market value is approximately US$1000 kg−1. However, traditional ectoine production in high-salinity media causes high costs of equipment loss and wastewater treatment. There is a growing attention to reduce the salinity of the fermentation broth without sacrificing the production of ectoine. Thus, heterologous production of ectoine in nonhalophilic microorganisms may represent the new generation of the industrial production of ectoine. In this review, we summarized and discussed the biological activities of ectoine on cell and human health protection and its heterologous production.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abdel-Aziz H, Wadie W, Abdallah DM, Lentzen G, Khayyal MT (2013) Novel effects of ectoine, a bacteria-derived natural tetrahydropyrimidine, in experimental colitis. Phytomedicine 20:585–591

    Article  CAS  PubMed  Google Scholar 

  • Becker J, Wittmann C (2020) Microbial production of extremolytes—high-value active ingredients for nutrition, health care, and well-being. Cur Opin Biotechnol 65:118–128

    Article  CAS  Google Scholar 

  • Becker J, Zelder O, Hafner S, Schroder H, Wittmann C (2011) From zero to hero–design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production. Metab Eng 13:159–168

    Article  CAS  PubMed  Google Scholar 

  • Becker J, Schäfer R, Kohlstedt M, Harder BJ, Borchert NS, Stöveken N, Bremer E, Wittmann C (2013) Systems metabolic engineering of Corynebacterium glutamicum for production of the chemical chaperone ectoine. Microb Cell Fact 12:110

    Article  PubMed  PubMed Central  Google Scholar 

  • Bethlehem L, van Echten-Deckert G (2021) Ectoines as novel anti-inflammatory and tissue protective lead compounds with special focus on inflammatory bowel disease and lung inflammation. Pharmacol Res 164:105389

    Article  CAS  PubMed  Google Scholar 

  • Beyer N, Driller H, Bünger J (2000) Ectoin—a innovative, multi-functional active substance for the cosmetic industry. Sofw Journal 126:27–29

    Google Scholar 

  • Bilstein A, Heinrich A, Rybachuk A, Mosges R (2021) Ectoine in the treatment of irritations and inflammations of the eye surface. Biomed Res Int 2021:8885032

    Article  PubMed  PubMed Central  Google Scholar 

  • Bissoyi A, Pramanik K (2013) Effects of non-toxic cryoprotective agents on the viability of cord blood derived mncs. CryoLetters 34:453–465

    CAS  PubMed  Google Scholar 

  • Booth IR (2014) Bacterial mechanosensitive channels: progress towards an understanding of their roles in cell physiology. Curr Opin Microbiol 18:16–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Botta C, Di Giorgio C, Sabatier AS, De Meo M (2008) Genotoxicity of visible light (400–800 nm) and photoprotection assessment of ectoin, l-ergothioneine and mannitol and four sunscreens. J Photochem Photobiol B 91:24–34

    Article  CAS  PubMed  Google Scholar 

  • Bownik A, Stepniewska Z (2016) Ectoine as a promising protective agent in humans and animals. Arh Hig Rada Toksikol 67:260–265

    Article  CAS  PubMed  Google Scholar 

  • Brands S, Schein P, Castro-Ochoa KF, Galinski EA (2019) Hydroxyl radical scavenging of the compatible solute ectoine generates two N-acetimides. Arch Biochem Biophys 674:108097

    Article  CAS  PubMed  Google Scholar 

  • Buenger J, Driller H (2004) Ectoin: an effective natural substance to prevent UVA-induced premature photoaging. Skin Pharmacol Phys 17:232–237

    Article  CAS  Google Scholar 

  • Bujak T, Zagorska-Dziok M, Niziol-Lukaszewska Z (2020) Complexes of ectoine with the anionic surfactants as active ingredients of cleansing cosmetics with reduced irritating potential. Molecules 25:1433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bursy J, Pierik AJ, Pica N, Bremer E (2007) Osmotically induced synthesis of the compatible solute hydroxyectoine is mediated by an evolutionarily conserved ectoine hydroxylase. J Biol Chem 282:31147–31155

    Article  CAS  PubMed  Google Scholar 

  • Castro-Ochoa KF, Vargas-Robles H, Chanez-Paredes S, Felipe-Lopez A, Cabrera-Silva RI, Shibayama M, Betanzos A, Nava P, Galinski EA, Schnoor M (2019) Homoectoine protects against colitis by preventing a Claudin switch in epithelial tight junctions. Dig Dis Sci 64:409–420

    Article  CAS  PubMed  Google Scholar 

  • Chen W, Zhang S, Jiang P-X, Yao J, He Y-Z, Chen L-C, Gui X-W, Dong Z-Y, Tang S-Y (2015) Design of an ectoine-responsive AraC mutant and its application in metabolic engineering of ectoine biosynthesis. Metab Eng 30:149–155

    Article  PubMed  Google Scholar 

  • Chen J, Liu P-F, Chu X-H, Chen J-W, Zhang H-W, Rowley DC, Wang H (2020) Metabolic pathway construction and optimization of escherichia coli for high-level ectoine production. Curr Microbiol 77:1412–1418

    Article  CAS  PubMed  Google Scholar 

  • Chung YC, Kim M-J, Kang EY, Kim YB, Kim BS, Park S-M, Hyun C-G (2019) Anti-melanogenic effects of hydroxyectoine via MITF inhibition by JNK, p38, and AKT pathways in B16F10 melanoma cells. Nat Prod Commun 14:1–6

    CAS  Google Scholar 

  • Correa A, Jhonny E (2013) Hydroxyectoine metabolism in halomonas elongata. Universitäts-und Landesbibliothek Bonn 3190

  • Cox CD, Bavi N, Martinac B (2018) Bacterial Mechanosensors. Annu Rev Physiol 80:71–93

    Article  CAS  PubMed  Google Scholar 

  • Czech L, Stoveken N, Bremer E (2016) EctD-mediated biotransformation of the chemical chaperone ectoine into hydroxyectoine and its mechanosensitive channel-independent excretion. Microb Cell Fact 15:126

    Article  PubMed  PubMed Central  Google Scholar 

  • Czech L, Hermann L, Stoveken N, Richter AA, Hoppner A, Smits SHJ, Heider J, Bremer E (2018) Role of the extremolytes ectoine and hydroxyectoine as stress protectants and nutrients: genetics, phylogenomics, biochemistry, and structural analysis. Genes (basel) 9:177

    Article  PubMed  Google Scholar 

  • Czech L, Hoppner A, Kobus S, Seubert A, Riclea R, Dickschat JS, Heider J, Smits SHJ, Bremer E (2019a) Illuminating the catalytic core of ectoine synthase through structural and biochemical analysis. Sci Rep 9:364

    Article  PubMed  PubMed Central  Google Scholar 

  • Czech L, Wilcken S, Czech O, Linne U, Brauner J, Smits SHJ, Galinski EA, Bremer E (2019b) Exploiting substrate promiscuity of ectoine hydroxylase for regio- and stereoselective modification of homoectoine. Front Microbiol 10:2745

    Article  PubMed  PubMed Central  Google Scholar 

  • Dao VA, Overhagen S, Bilstein A, Kolot C, Sonnemann U, Mosges R (2019) Ectoine lozenges in the treatment of acute viral pharyngitis: a prospective, active-controlled clinical study. Eur Arch Otorhinolaryngol 276:775–783

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Gioacchino M, Bruni F, Sodo A, Imberti S, Ricci MA (2019) Ectoine hydration, aggregation and influence on water structure. Mol Phys 117:3311–3319

    Article  Google Scholar 

  • Dong Y-S, Zhang H, Wang X-Y, Ma J-J, Lei P, Xu H, Li S (2021) Enhancing ectoine production by recombinant Escherichia coli through step-wise fermentation optimization strategy based on kinetic analysis. Bioproc Biosyst Eng 44:1557–1566

    Article  CAS  Google Scholar 

  • Dwivedi M, Brinkkotter M, Harishchandra RK, Galla HJ (2014) Biophysical investigations of the structure and function of the tear fluid lipid layers and the effect of ectoine. Part B: artificial lipid films. BBA-Biomembranes 1838:2716–2727

    Article  CAS  PubMed  Google Scholar 

  • Eiberweiser A, Nazet A, Kruchinin SE, Fedotova MV, Buchner R (2015) Hydration and ion binding of the osmolyte ectoine. J Phys Chem B 119:15203–15211

    Article  CAS  PubMed  Google Scholar 

  • Eichel A, Bilstein A, Werkhauser N, Mosges R (2014) Meta-analysis of the efficacy of ectoine nasal spray in patients with allergic rhinoconjunctivitis. J Allergy, p 292545

  • Eilert E, Kranz A, Hollenberg CP, Piontek M, Suckow M (2013) Synthesis and release of the bacterial compatible solute 5-hydroxyectoine in Hansenula polymorpha. J Biotechnol 167:85–93

    Article  CAS  PubMed  Google Scholar 

  • El Assal R, Guven S, Gurkan UA, Gozen I, Shafiee H, Dalbeyler S, Abdalla N, Thomas G, Fuld W, Illigens BMW, Estanislau J, Khoory J, Kaufman R, Zylberberg C, Lindeman N, Wen Q, Ghiran I, Demirci U (2014) Bio-inspired cryo-ink preserves red blood cell phenotype and function during nanoliter vitrification. Adv Mater 26:5815–5822

    Article  PubMed  PubMed Central  Google Scholar 

  • Fedotova M (2019) Compatible osmolytes-bioprotectants: is there a common link between their hydration and their protective action under abiotic stresses? J Mol Liq 292:111339

    Article  CAS  Google Scholar 

  • Fenizia S, Thume K, Wirgenings M, Pohnert G (2020) Ectoine from bacterial and algal origin is a compatible solute in microalgae. Mar Drugs 18:42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galinski EA, Pfeiffer HP, Troper HG (1985) 1,4,5,6-Tetrahydro-2-methyl-4-pyrimidinecarboxylic acid A novel cyclic amino acid from halophilic phototrophic bacteria of the genus Ectothiorhodospira. Eur J Biochem 149:135–139

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Estepa R, Argandona M, Reina-Bueno M, Capote N, Iglesias-Guerra F, Nieto JJ, Vargas C (2006) The ectD gene, which is involved in the synthesis of the compatible solute hydroxyectoine, is essential for thermoprotection of the halophilic bacterium Chromohalobacter salexigens. J Bacteriol 188:3774–3784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Georgi T, Rittmann D, Wendisch VF (2005) Lysine and glutamate production by Corynebacterium glutamicum on glucose, fructose and sucrose: roles of malic enzyme and fructose-1,6-bisphosphatase. Metab Eng 7:291–301

    Article  CAS  PubMed  Google Scholar 

  • Giesselmann G, Dietrich D, Jungmann L, Kohlstedt M, Jeon EJ, Yim SS, Sommer F, Zimmer D, Muhlhaus T, Schroda M, Jeong KJ, Becker J, Wittmann C (2019) Metabolic engineering of Corynebacterium glutamicum for high-level ectoine production: design, combinatorial assembly, and implementation of a transcriptionally balanced heterologous ectoine pathway. Biotechnol J 14:1800417

    Article  Google Scholar 

  • Goraj W, Stępniewska Z, Szafranek-Nakonieczna A (2019) Biosynthesis and the possibility of using ectoine and hydroxyectoine in health care. Adv Microbiol Postepy Mikrobiologii 58:339–349

    Google Scholar 

  • Graf R, Anzali S, Buenger J, Pfluecker F, Driller H (2008) The multifunctional role of ectoine as a natural cell protectant. Clin Dermatol 26:326–333

    Article  PubMed  Google Scholar 

  • Grether-Beck S, Timmer A, Felsner I, Brenden H, Brammertz D, Krutmann J (2005) Ultraviolet a-induced signaling involves a ceramide-mediated autocrine loop leading to ceramide de novo synthesis. J Invest Dermatol 125:545–553

    Article  CAS  PubMed  Google Scholar 

  • Hahn MB, Solomun T, Wellhausen R, Hermann S, Seitz H, Meyer S, Kunte HJ, Zeman J, Uhlig F, Smiatek J, Sturm H (2015) Influence of the compatible solute ectoine on the local water structure: Implications for the binding of the protein G5P to DNA. J Phys Chem B 119:15212–15220

    Article  CAS  PubMed  Google Scholar 

  • Hahn MB, Uhlig F, Solomun T, Smiatek J, Sturm H (2016) Combined influence of ectoine and salt: spectroscopic and numerical evidence for compensating effects on aqueous solutions. Phys Chem Chem Phys 18:28398–28402

    Article  CAS  PubMed  Google Scholar 

  • Hahn MB, Meyer S, Schroter MA, Kunte HJ, Solomun T, Sturm H (2017) DNA protection by ectoine from ionizing radiation: molecular mechanisms. Phys Chem Chem Phys 19:25717–25722

    Article  CAS  PubMed  Google Scholar 

  • Harishchandra RK, Wulff S, Lentzen G, Neuhaus T, Galla HJ (2010) The effect of compatible solute ectoines on the structural organization of lipid monolayer and bilayer membranes. Biophys Chem 150:37–46

    Article  CAS  PubMed  Google Scholar 

  • Harishchandra RK, Sachan AK, Kerth A, Lentzen G, Neuhaus T, Galla HJ (2011) Compatible solutes: ectoine and hydroxyectoine improve functional nanostructures in artificial lung surfactants. BBA-Biomembranes 1808:2830–2840

    Article  CAS  PubMed  Google Scholar 

  • He Y, Gong J, Yu H, Tao Y, Zhang S, Dong Z (2015) High production of ectoine from aspartate and glycerol by use of whole-cell biocatalysis in recombinant Escherichia coli. Microb Cell Fact 14:55

    Article  PubMed  PubMed Central  Google Scholar 

  • Hermann L, Mais CN, Czech L, Smits SHJ, Bange G, Bremer E (2020) The ups and downs of ectoine: structural enzymology of a major microbial stress protectant and versatile nutrient. Biol Chem 401:1443–1468

    Article  CAS  PubMed  Google Scholar 

  • Herzog M, Dwivedi M, Harishchandra RK, Bilstein A, Galla HJ, Winter R (2019) Effect of ectoine, hydroxyectoine and beta-hydroxybutyrate on the temperature and pressure stability of phospholipid bilayer membranes of different complexity. Colloids Surf, B 178:404–411

    Article  CAS  Google Scholar 

  • Hillier HT, Altermark B, Leiros I (2020) The crystal structure of the tetrameric DABA-aminotransferase EctB, a rate-limiting enzyme in the ectoine biosynthesis pathway. FEBS J 287:4641–4658

    Article  CAS  PubMed  Google Scholar 

  • Hirasawa T, Shimizu H (2016) Recent advances in amino acid production by microbial cells. Curr Opin Biotechnol 42:133–146

    Article  CAS  PubMed  Google Scholar 

  • Hoppner A, Widderich N, Lenders M, Bremer E, Smits SH (2014) Crystal structure of the ectoine hydroxylase, a snapshot of the active site. J Biol Chem 289:29570–29583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hseu Y-C, Chen X-Z, Vudhya Gowrisankar Y, Yen HR, Chuang J-Y, Yang H-L (2020) The skin-whitening effects of ectoine via the suppression of α-MSH-stimulated melanogenesis and the activation of antioxidant Nrf2 pathways in UVA-irradiated keratinocytes. Antioxidants (basel) 9:63

    Article  CAS  PubMed  Google Scholar 

  • Inbar L, Lapidot A (1988) The structure and biosynthesis of new tetrahydropyrimidine derivatives in actinomycin D producer Streptomyces parvulus. Use of 13C- and 15N-labeled l-glutamate and 13C and 15N NMR spectroscopy. J Biol Chem 263:16014–16022

    Article  CAS  PubMed  Google Scholar 

  • Jebbar M, Talibart R, Gloux K, Bernard T, Blanco C (1992) Osmoprotection of Escherichia coli by ectoine: uptake and accumulation characteristics. Journal of Bacteriololgy 174:5027–5035

    Article  CAS  Google Scholar 

  • Kalinowski J, Bathe B, Bartels D, Bischoff N, Bott M, Burkovski A, Dusch N, Eggeling L, Eikmanns BJ, Gaigalat L, Goesmann A, Hartmann M, Huthmacher K, Kramer R, Linke B, McHardy AC, Meyer F, Mockel B, Pfefferle W, Puhler A, Rey DA, Ruckert C, Rupp O, Sahm H, Wendisch VF, Wiegrabe I, Tauch A (2003) The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its impact on the production of l-aspartate-derived amino acids and vitamins. J Biotechnol 104:5–25

    Article  CAS  PubMed  Google Scholar 

  • Kanapathipillai M, Lentzen G, Sierks M, Park CB (2005) Ectoine and hydroxyectoine inhibit aggregation and neurotoxicity of Alzheimer’s β-amyloid. FEBS Lett 579:4775–4780

    Article  CAS  PubMed  Google Scholar 

  • Kauth M, Trusova OV (2022) Topical ectoine application in children and adults to treat inflammatory diseases associated with an impaired skin barrier: a systematic review. Dermatol Ther 12:295–313

    Article  Google Scholar 

  • Kim HM, Heinzle E, Wittmann C (2006) Deregulation of aspartokinase by single nucleotide exchange leads to global flux rearrangement in the central metabolism of Corynebacterium glutamicum. J Microbiol Biotechnol 16:1174–1179

    CAS  Google Scholar 

  • Kolp S, Pietsch M, Galinski EA, Gutschow M (2006) Compatible solutes as protectants for zymogens against proteolysis. Biochim Biophys Acta 1764:1234–1242

    Article  CAS  PubMed  Google Scholar 

  • Kunte HJ, Lentzen G, Galinski EA (2014) Industrial production of the cell protectant ectoine protection mechanisms, processes, and products. Curr Biotechnol 3:10–25

    Article  CAS  Google Scholar 

  • Lang Y, Bai L, Ren Y, Zhang L, Nagata S (2011) Production of ectoine through a combined process that uses both growing and resting cells of Halomonas salina DSM 5928T. Extremophiles 15:303–310

    Article  CAS  PubMed  Google Scholar 

  • Lapidot A, Benasher E, Eisenstein M (1995) Tetrahydropyrimidine derivatives inhibit binding of a Tat-like, arginine-containing peptide, to HIV TAR RNA in vitro. FEBS Lett 367:33–38

    Article  CAS  PubMed  Google Scholar 

  • Lee KH, Park JH, Kim TY, Kim HU, Lee SY (2007) Systems metabolic engineering of Escherichia coli for l-threonine production. Mol Syst Biol 3:149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu M-S, Liu H, Shi M, Jiang M-Y, Li L-L, Zheng Y-N (2021) Microbial production of ectoine and hydroxyectoine as high-value chemicals. Microb Cell Fact 20:76

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lo CC, Bonner CA, Xie G, D’Souza M, Jensen RA (2009) Cohesion group approach for evolutionary analysis of aspartokinase, an enzyme that feeds a branched network of many biochemical pathways. Microbiol Mol Biol Rev 73:594–651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Louis P, Galinski EA (1997) Characterization of genes for the biosynthesis of the compatible solute ectoine from Marinococcus halophilus and osmoreg u lated expression in Escherichia coli. Microbiology 143:1141–1149

    Article  CAS  PubMed  Google Scholar 

  • Ma H, Zhao Y-Q, Huang W-Z, Zhang L-Z, Wu F-Q, Ye J-W, Chen G-Q (2020) Rational flux-tuning of Halomonas bluephagenesis for co-production of bioplastic PHB and ectoine. Nat Commun 11:3313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mais CN, Hermann L, Altegoer F, Seubert A, Richter AA, Wernersbach I, Czech L, Bremer E, Bange G (2020) Degradation of the microbial stress protectants and chemical chaperones ectoine and hydroxyectoine by a bacterial hydrolase-deacetylase complex. J Biol Chem 295:9087–9104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marrot L, Jones C, Perez P, Meunier JR (2008) The significance of Nrf2 pathway in (photo)-oxidative stress response in melanocytes and keratinocytes of the human epidermis. Pigment Cell Melanoma R 21:79–88

    Article  CAS  Google Scholar 

  • Meyer S, Schroter MA, Hahn MB, Solomun T, Sturm H, Kunte HJ (2017) Ectoine can enhance structural changes in DNA in vitro. Sci Rep 7:7170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mukherjee S, Edmunds M, Lei X-G, Ottaviani MF, Ananthapadmanabhan KP, Turro NJ (2010) Stearic acid delivery to corneum from a mild and moisturizing cleanser. J Cosmet Dermatol 9:202–210

    Article  PubMed  Google Scholar 

  • Nayak PK, Goode M, Chang DP, Rajagopal K (2020) Ectoine and hydroxyectoine stabilize antibodies in spray-dried formulations at elevated temperature and during a freeze/thaw process. Mol Pharm 17:3291–3297

    Article  CAS  PubMed  Google Scholar 

  • Ning Y, Wu X, Zhang C, Xu Q, Chen N, Xie X (2016) Pathway construction and metabolic engineering for fermentative production of ectoine in Escherichia coli. Metab Eng 36:10–18

    Article  CAS  PubMed  Google Scholar 

  • Nosch DS, Joos RE, Job M (2021) Prospective randomized study to evaluate the efficacy and tolerability of Ectoin® containing Eye Spray (EES09) and comparison to the liposomal Eye Spray Tears Again® (TA) in the treatment of dry eye disease. Cont Lens Anterior Eye 44:101318

    Article  PubMed  Google Scholar 

  • Ono H, Sawada K, Khunajakr N, Tao T, Yamamoto M, Hiramoto M, Shinmyo A, Takano M, Murooka Y (1999) Characterization of biosynthetic enzymes for ectoine as a compatible solute in a moderately halophilic eubacterium, Halomonas elongata. Journal of Bacteriololgy 181:91–99

    Article  CAS  Google Scholar 

  • Oprzeska-Zingrebe EA, Meyer S, Roloff A, Kunte HJ, Smiatek J (2018) Influence of compatible solute ectoine on distinct DNA structures: thermodynamic insights into molecular binding mechanisms and destabilization effects. Phys Chem Chem Phys 20:25861–25874

    Article  CAS  PubMed  Google Scholar 

  • Pastor JM, Salvador M, Argandona M, Bernal V, Reina-Bueno M, Csonka LN, Iborra JL, Vargas C, Nieto JJ, Canovas M (2010) Ectoines in cell stress protection: uses and biotechnological production. Biotechnol Adv 28:782–801

    Article  CAS  PubMed  Google Scholar 

  • Perez-Garcia F, Ziert C, Risse JM, Wendisch VF (2017) Improved fermentative production of the compatible solute ectoine by Corynebacterium glutamicum from glucose and alternative carbon sources. J Biotechnol 258:59–68

    Article  CAS  PubMed  Google Scholar 

  • Pliotas C, Naismith JH (2017) Spectator no more, the role of the membrane in regulating ion channel function. Curr Opin Struct Biol 45:59–66

    Article  CAS  PubMed  Google Scholar 

  • Rabe JH, Mamelak AJ, Mcelgunn PJ, Morison WL, Sauder DN (2006) Photoaging: mechanisms and repair. J Am Acad Dermatol 55:1–19

    Article  PubMed  Google Scholar 

  • Rasmussen T (2016) How do mechanosensitive channels sense membrane tension? Biochem Soc Trans 44:1019–1025

    Article  CAS  PubMed  Google Scholar 

  • Reshetnikov AS, Rozova ON, Trotsenko YA, But SY, Khmelenina VN, Mustakhimov II (2020) Ectoine degradation pathway in halotolerant methylotrophs. PLoS ONE 15:0232244

    Article  Google Scholar 

  • Reuter K, Pittelkow M, Bursy J, Heine A, Craan T, Bremer E (2010) Synthesis of 5-hydroxyectoine from ectoine: crystal structure of the non-heme iron(II) and 2-oxoglutarate-dependent dioxygenase EctD. PLoS ONE 5:10647

    Article  Google Scholar 

  • Richter AA, Mais CN, Czech L, Geyer K, Hoeppner A, Smits SHJ, Erb TJ, Bange G, Bremer E (2019) Biosynthesis of the stress-protectant and chemical chaperon ectoine: biochemistry of the transaminase EctB. Front Microbiol 10:2811

    Article  PubMed  PubMed Central  Google Scholar 

  • Rousseau K, Kauser S, Pritchard LE, Warhurst A, Oliver RL, Slominski A, Wei ET, Thody AJ, Tobin DJ, White A (2007) Proopiomelanocortin (POMC), the ACTH/melanocortin precursor, is secreted by human epidermal keratinocytes and melanocytes and stimulates melanogenesis. FASEB J 21:1844–1856

    Article  CAS  PubMed  Google Scholar 

  • Ryu J, Kanapathipillai M, Lentzen G, Park CB (2008) Inhibition of β-amyloid peptide aggregation and neurotoxicity by α-D-mannosylglycerate, a natural extremolyte. Peptides 29:578–584

    Article  CAS  PubMed  Google Scholar 

  • Sahle CJ, Schroer MA, Jeffries CM, Niskanen J (2018) Hydration in aqueous solutions of ectoine and hydroxyectoine. Phys Chem Chem Phys 20:27917–27923

    Article  CAS  PubMed  Google Scholar 

  • Sajjad W, Qadir S, Ahmad M, Rafiq M, Hasan F, Tehan R, McPhail KL, Shah AA (2018) Ectoine: a compatible solute in radio-halophilic Stenotrophomonas sp. WMA-LM19 strain to prevent ultraviolet-induced protein damage. J Appl Microbiol 125:457–467

    Article  CAS  PubMed  Google Scholar 

  • Salapatek A, Bate M, Bilstein A, Patel D (2011) Ectoin®, a novel, non-drug, extremophile-based device, relieves allergic rhinoconjunctivitis symptoms in patients in an environmental exposure chamber model. J Allergy Clin Immun 127:AB202

    Article  Google Scholar 

  • Sauer T, Galinski EA (1997) Bacterial milking: a novel bioprocess for production of compatible solutes. Biotechnol Bioeng 57:306–313

    Article  Google Scholar 

  • Schroter MA, Meyer S, Hahn MB, Solomun T, Sturm H, Kunte HJ (2017) Ectoine protects DNA from damage by ionizing radiation. Sci Rep 7:15272

    Article  PubMed  PubMed Central  Google Scholar 

  • Schulz A, Stoveken N, Binzen IM, Hoffmann T, Heider J, Bremer E (2017) Feeding on compatible solutes: a substrate-induced pathway for uptake and catabolism of ectoines and its genetic control by EnuR. Environ Microbiol 19:926–946

    Article  CAS  PubMed  Google Scholar 

  • Schwibbert K, Marin-Sanguino A, Bagyan I, Heidrich G, Lentzen G, Seitz H, Rampp M, Schuster SC, Klenk HP, Pfeiffer F, Oesterhelt D, Kunte HJ (2011) A blueprint of ectoine metabolism from the genome of the industrial producer Halomonas elongata DSM 2581T. Environ Microbiol 13:1973–1994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shamsollahi HR, Ghoochani M, Jaafari J, Moosavi A, Sillanpaa M, Alimohammadi M (2019) Environmental exposure to endotoxin and its health outcomes: a systematic review. Ecotox Environ Safe 174:236–244

    Article  CAS  Google Scholar 

  • Song CW, Lee J, Ko YS, Lee SY (2015) Metabolic engineering of Escherichia coli for the production of 3-aminopropionic acid. Metab Eng 30:121–129

    Article  CAS  PubMed  Google Scholar 

  • Sonnemann U, Scherner O, Werkhauser N (2014) Treatment of rhinitis sicca anterior with ectoine containing nasal spray. J Allergy 2014:273219

    Article  Google Scholar 

  • Srinivasan PK, Fet N, Bleilevens C, Afify M, Doorschodt B, Yagi S, van Echten-Deckert G, Tolba RH (2014) Hydroxyectoine ameliorates preservation injury in deceased after cardiac death donors in experimental liver grafts. Ann Transplant 19:165–173

    Article  CAS  Google Scholar 

  • Strong PJ, Kalyuzhnaya M, Silverman J, Clarke WP (2016) A methanotroph-based biorefinery: potential scenarios for generating multiple products from a single fermentation. Bioresour Technol 215:314–323

    Article  CAS  PubMed  Google Scholar 

  • Sydlik U, Gallitz I, Albrecht C, Abel J, Krutmann J, Unfried K (2009) The compatible solute ectoine protects against nanoparticle-induced neutrophilic lung inflammation. Am J Respir Crit Care Med 180:29–35

    Article  CAS  PubMed  Google Scholar 

  • Sydlik U, Peuschel H, Paunel-Gorgulu A, Keymel S, Kramer U, Weissenberg A, Kroker M, Seghrouchni S, Heiss C, Windolf J, Bilstein A, Kelm M, Krutmann J, Unfried K (2013) Recovery of neutrophil apoptosis by ectoine: a new strategy against lung inflammation. Eur Respir J 41:433–442

    Article  CAS  PubMed  Google Scholar 

  • Tsai T, Mueller-Buehl AM, Satgunarajah Y, Kuehn S, Dick HB, Joachim SC (2020) Protective effect of the extremolytes ectoine and hydroxyectoine in a porcine organ culture. Graefes Arch Clin Exp Ophthalmol 258:2185–2203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsuge Y, Matsuzawa H (2021) Recent progress in production of amino acid-derived chemicals using Corynebacterium glutamicum. World J Microb Biot 37:49

    Article  CAS  Google Scholar 

  • Unfried K, Kroker M, Autengruber A, Gotic M, Sydlik U (2014) The compatible solute ectoine reduces the exacerbating effect of environmental model particles on the immune response of the airways. J Allergy 2014:708458

    Article  Google Scholar 

  • Werkhauser N, Bilstein A, Sonnemann U (2014) Treatment of allergic rhinitis with ectoine containing nasal spray and eye drops in comparison with azelastine containing nasal spray and eye drops or with cromoglycic acid containing nasal spray. J Allergy 2014:176597

    Article  Google Scholar 

  • Widderich N, Czech L, Elling FJ, Konneke M, Stoveken N, Pittelkow M, Riclea R, Dickschat JS, Heider J, Bremer E (2016a) Strangers in the archaeal world: osmostress-responsive biosynthesis of ectoine and hydroxyectoine by the marine thaumarchaeon Nitrosopumilus maritimus. Environ Microbiol 18:1227–1248

    Article  CAS  PubMed  Google Scholar 

  • Widderich N, Kobus S, Hoppner A, Riclea R, Seubert A, Dickschat JS, Heider J, Smits SH, Bremer E (2016b) Biochemistry and crystal structure of ectoine synthase: a metal-containing member of the cupin superfamily. PLoS ONE 11:0151285

    Article  Google Scholar 

  • Wittmar J, Meyer S, Sieling T, Kunte J, Smiatek J, Brand I (2020) What does ectoine do to DNA? A molecular-scale picture of compatible solute-biopolymer interactions. J Phys Chem B 124:7999–8011

    Article  CAS  PubMed  Google Scholar 

  • Yang S, Liu Q-T, Zhang Y-F, Du G-C, Chen J, Kang Z (2018) Construction and characterization of broad-spectrum promoters for synthetic biology. ACS Synth Biol 7:287–291

    Article  CAS  PubMed  Google Scholar 

  • Yao C-L, Lin Y-M, Mohamed MS, Chen J-H (2013) Inhibitory effect of ectoine on melanogenesis in B16–F0 and A2058 melanoma cell lines. Biochem Eng J 78:163–169

    Article  CAS  Google Scholar 

  • Yu I, Jindo Y, Nagaoka M (2007) Microscopic understanding of preferential exclusion of compatible solute ectoine. J Phys Chem B 111:10231–10238

    Article  CAS  PubMed  Google Scholar 

  • Zaccai G, Bagyan I, Combet J, Cuello GJ, Deme B, Fichou Y, Gallat FX, Galvan Josa VM, von Gronau S, Haertlein M, Martel A, Moulin M, Neumann M, Weik M, Oesterhelt D (2016) Neutrons describe ectoine effects on water H-bonding and hydration around a soluble protein and a cell membrane. Sci Rep 6:31434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Q, Li S-N, Lv P-W, Sun S-M, Ma C-Q, Xu P, Su H-J, Yang C-Y (2019) High ectoine production by an engineered Halomonas hydrothermalis Y2 in a reduced salinity medium. Microb Cell Fact 18:184

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grant No. 32102099) and Natural Science Foundation of Zhejiang Province (Grant No. Q22C207891) and the China Postdoctoral Science Foundation (Grant No. 2021M702895). We highly appreciate Ziyi Cheng (University of Toronto) for the language polish and revision.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiaolong Chen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest in the publication.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, Z., Wu, C., Zhu, L. et al. Bioactivity profiling of the extremolyte ectoine as a promising protectant and its heterologous production. 3 Biotech 12, 331 (2022). https://doi.org/10.1007/s13205-022-03370-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13205-022-03370-5

Keywords

Navigation