Ectoine is an important natural secondary metabolite in halophilic microorganisms. It protects cells against environmental stressors, such as salinity, freezing, drying, and high temperatures. Ectoine is widely used in medical, cosmetic, and other industries. Due to the commercial market demand of ectoine, halophilic microorganisms are the primary method for producing ectoine, which is produced using the industrial fermentation process "bacterial milking." The method has some limitations, such as the high salt concentration fermentation, which is highly corrosive to the equipment, and this also increases the difficulty of downstream purification and causes high production costs. The ectoine synthesis gene cluster has been successfully heterologously expressed in industrial microorganisms, and the yield of ectoine was significantly increased and the cost was reduced. This review aims to summarize and update microbial production of ectoine using different microorganisms, environments, and metabolic engineering and fermentation strategies and provides important reference for the development and application of ectoine.

Anhui Engineering Research Center for Eco Agriculture of Traditional Chinese Medicine West Anhui University Lu'an 23702 China

Anhui Province Key Laboratory for Quality Evaluationand Improvement of Traditional Chinese Medicine West Anhui University Lu 237012 China

College of Biotechnology and Pharmaceutical Engineering West Anhui University Lu'an 237012 China

Key Laboratory of Marine Ecosystem and Biogeochemistry Ministry of Natural Resources State Oceanic Administration and 2nd Institute of Oceanography Hangzhou 310012 China

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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. https://doi.org/10.1016/j.phymed.2013.01.009 DOI

Abdel-Aziz H, Wadie W, Scherner O, Efferth T, Khayyal MT (2015) Bacteria-derived compatible solutes ectoine and 5α-hydroxyectoine act as intestinal barrier stabilizers to ameliorate experimental inflammatory bowel disease. J Nat Prod 78:1309–1315. https://doi.org/10.1021/acs.jnatprod.5b00115 DOI

Adam B, Zofia S, Tadeusz S (2014) Protective effects of ectoine on heat-stressed Daphnia magna. J Comp Physiol B 184:961–976. https://doi.org/10.1007/s00360-014-0860-x DOI

Adamiak J, Bonifay V, Otlewska A, Sunner JA, Beech IB, Stryszewska T, Kanka S, Oracz J, Zyzelewicz D, Gutarowska B (2017) Untargeted metabolomics approach in halophiles: understanding the biodeterioration process of building materials. Front Microbiol 8:2448. https://doi.org/10.3389/fmicb.2017.02448 DOI

Anburajan L, Meena B, Sreelatha T, Vinithkumar NV, Kirubagaran R, Dharani G (2019) Ectoine biosynthesis genes from the deep sea halophilic eubacteria, Bacillus clausii NIOT-DSB04: its molecular and biochemical characterization. Microb Pathog 136:103693. https://doi.org/10.1016/j.micpath.2019.103693 DOI

Arahal DR, García MT, Vargas C, Canovas D, Nieto JJ, Ventosa A (2001) Chromohalobacter salexigens sp. nov., a moderately halophilic species that includes Halomonas elongata DSM 3043 and ATCC 33174. In J Syst Evol Microbiol 51:1457–1462. https://doi.org/10.1099/00207713-51-4-1457 DOI

Autengruber A, Sydlik U, Kroker M, Hornstein T, Ale-Agha N, Stöckmann D, Bilstein A, Albrecht C, Paunel-Görgülü A, Suschek CV, Krutmann J, Unfried K (2014) Signalling-dependent adverse health effects of carbon nanoparticles are prevented by the compatible solute mannosylglycerate (Firoin) in vitro and in vivo. PLoS ONE 9:e111485. https://doi.org/10.1371/journal.pone.0111485 DOI

Bazazzadegan N, Shasaltaneh MD, Saliminejad K, Kamali K, Banan M, Nazari R, Riazi GH, Khorram Khorshid HR (2017) Effects of ectoine on behavior and candidate genes expression in ICV-STZ rat model of sporadic Alzheimer’s disease. Adv Pharm Bull 7:629–636. https://doi.org/10.15171/apb.2017.075

Behazin R, Ebrahimi A (2018) The physicochemical properties and tyrosinase inhibitory activity of ectoine and its analogues: a theoretical study. Comput Theor Chem 1130:6–14. https://doi.org/10.1016/j.comptc.2018.03.003

Bestvater T, Louis P, Galinski EA (2008) Heterologous ectoine production in Escherichia coli: by-passing the metabolic bottle-neck. Saline Syst 4:12. https://doi.org/10.1186/1746-1448-4-12 DOI

Boroujeni MB, Nayeri H (2018) Stabilization of bovine lactoperoxidase in the presence of ectoine. Food Chem 265:208–215. https://doi.org/10.1016/j.foodchem.2018.05.067 DOI

Boscolo B, Leal SS, Ghibaudi EM, Gomes CM (2007) Lactoperoxidase folding and catalysis relies on the stabilization of the alpha-helix rich core domain: a thermal unfolding study. Biochim Biophys Acta Proteins Proteomics 1774:1164–1172. https://doi.org/10.1016/j.bbapap.2007.07.003 DOI

Bownik A (2016) Protective effects of ectoine on physiological parameters of Daphnia Magna subjected to clove oil-induced anaesthesia. Turk J Fish Aquat Sci 16:691–701. https://doi.org/10.4194/1303-2712-v16_3_23 DOI

Bownik A, Stepniewska Z (2015) Protective effects of bacterial osmoprotectant ectoine on bovine erythrocytes subjected to staphylococcal alpha-haemolysin. Toxicon 99:130–135. https://doi.org/10.1016/j.toxicon.2015.03.022 DOI

Bownik A, Stepniewska Z (2016) Ectoine as a promising protective agent in humans and animals. Arh Hig Rada Toksikol 67:260–265. https://doi.org/10.1515/aiht-2016-67-2837 DOI

Bownik A, Slaska B, Szabelak A (2018) Protective effects of compatible solute ectoine against ethanol-induced toxic alterations in Daphnia magna. J Comp Physiol B 188:779–791. https://doi.org/10.1007/s00360-018-1165-2 DOI

Cai L, Tan D, Aibaidula G, Dong XR, Chen JC, Tian WD, Chen GQ (2011) Comparative genomics study of polyhydroxyalkanoates (PHA) and ectoine relevant genes from Halomonas sp. TD01 revealed extensive horizontal gene transfer events and co-evolutionary relationships. Microb Cell Fact 10:88. https://doi.org/10.1186/1475-2859-10-88

Cantera S, Lebrero R, Sadornil L, García-Encina PA, Muñoz R (2016) Valorization of CH DOI

Cantera S, Lebrero R, Rodríguez E, García-Encina PA, Muñoz R (2017) Continuous abatement of methane coupled with ectoine production by Methylomicrobium alcaliphilum 20Z in stirred tank reactors: a step further towards greenhouse gas biorefineries. J Cleaner Prod 152:134–141. https://doi.org/10.1016/j.jclepro.2017.03.123 DOI

Cantera S, Muñoz R, Lebrero R, López JC, Rodríguez Y, García-Encina PA (2018) Technologies for the bioconversion of methane into more valuable products. Curr Opin Biotechol 50:128–135. https://doi.org/10.1016/j.copbio.2017.12.021 DOI

Chen W, Zhang S, Jiang PX, Yao J, He YZ, Chen LC, Gui XW, Dong ZY, Tang SY (2015) Design of an ectoine-responsive AraC mutant and its application in metabolic engineering of ectoine biosynthesis. Metab Eng 30:149–155. https://doi.org/10.1016/j.ymben.2015.05.004 DOI

Chen RF, Lv LH, Yao S, Zhu LJ, Li B, Qian JQ (2017) Purification of (S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4 carboxylic acid from halophiles. Biomed Res-India 28:5511–5518

Chen SY, Peng TC, Huang SZ, Chien CC (2022) Isolation of an ectoine-producing Sinobaca sp. and identification of genes that are involved in ectoine biosynthesis. FEMS Microbiol Lett 369: fnac046. https://doi.org/10.1093/femsle/fnac046

Choi JK, El Assal R, Ng N, Ginsburg E, Maas RL, Anchan RM, Demirci U (2018) Bio-inspired solute enables preservation of human oocytes using minimum volume vitrification. J Tissue Eng Regen Med 12:e142–e149. https://doi.org/10.1002/term.2439 DOI

Czech L, Stöveken 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. https://doi.org/10.12934/016-0525-4

Dao VA, Bilstein A, Overhagen S, Géczi L, Baráth Z, Mösges R (2018) Effectiveness, tolerability, and safety of ectoine-containing mouthwash versus those of a calcium phosphate mouthwash for the treatment of chemotherapy-induced oral mucositis: a prospective, active-controlled, non-interventional Study. Oncol Ther 6:59–72. https://doi.org/10.1007/s40487-018-0060-z DOI

Doan VT, Guzmán H, Mai TH, Hatti-Kaul R (2010) Ectoine production by Halomonas boliviensis: optimization using response surface methodology. Mar Biotechnol 12:586–593. https://doi.org/10.1007/s10126-009-9246-6 DOI

Doan VT, Hashim SO, Hatti-Kaul R, Mamo G (2013) Ectoine-mediated protection of enzyme from the effect of pH and temperature stress: a study using Bacillus halodurans xylanase as a model. Appl Microbiol Biot 97:6271–6278. https://doi.org/10.1007/s00253-012-4528-8 DOI

Dong YS, Zhang H, Wang XY, Ma JJ, Lei P, Xu H, Li S (2021) Enhancing ectoine production by recombinant Escherichia coli through step-wise fermentation optimization strategy based on kinetic analysis. Bioprocess Biosyst Eng 44:1557–1566. https://doi.org/10.1007/s00449-021-02541-7 DOI

Fallet C, Rohe P, Franco-Lara E (2010) Process optimization of the integrated synthesis and secretion of ectoine and hydroxyectoine under hyper/hypo-osmotic stress. Biotechnol Bioeng 107:124–133. https://doi.org/10.1002/bit.22750 DOI

Fischel U, Oren A (1993) Fate of compatible solutes during dilution stress in Ectothiorhodospira marismortui. Fems Microbiol Lett 113:113–118 DOI

Galinski EA, Pfeiffer HP, Trueper 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 149:135–140. https://doi.org/10.1111/j.1432-1033.1985.tb08903.x DOI

Genereux JC, Wiseman RL (2015) Regulating extracellular proteostasis capacity through the unfolded protein response. Prion 9:10–21. https://doi.org/10.1080/19336896.2015.1011887 DOI

Guo D, Ren C, Ali A, Zhang Y, Du J, Wang P, Li RH, Zhang ZQ (2020) A phytoextraction trial strengthened by Streptomyces pactum and plant nutrients: In view of plant bioindicators and phytoextraction indices. Environ Pollut 265:114867. https://doi.org/10.1016/j.envpol.2020.114867 DOI

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. https://doi.org/10.1021/acs.jpcb.5b09506 DOI

Han J, Gao QX, Zhang YG, Li L, Mohamad OAA, Rao MPN, Xiao M, Hozzein WN, Alkhalifah DHM, Tao Y, Li WJ (2018) Transcriptomic and ectoine analysis of halotolerant Nocardiopsis gilva YIM 90087(T) under salt stress. Front Microbiol 9:618. https://doi.org/10.3389/fmicb.2018.00618 DOI

Hazari YM, Habib M, Bashir S, Bashir A, Hilal N, Irfan S, Ul Haq E, Fazili KM (2016) Natural osmolytes alleviate GRP78 and ATF-4 levels: corroboration for potential modulators of unfolded protein response. Life Sci 146:148–153. https://doi.org/10.1016/j.lfs.2016.01.002 DOI

He YZ, Gong J, Yu HY, Tao Y, Zhang S, Dong ZY (2015) High production of ectoine from aspartate and glycerol by use of whole-cell biocatalysis in recombinant Escherichia coli. Microb Cell Fact 14:55. https://doi.org/10.1186/s12934-015-0238-0 DOI

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 DOI

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. https://doi.org/10.1016/j.febslet.2005.07.057 DOI

Kang JY, Lee B, Kim JA, Kim MS, Kim CH (2022) Identification and characterization of an ectoine biosynthesis gene cluster from Aestuariispira ectoiniformans sp. nov., isolated from seawater. Microbiol Res 254:126898. https://doi.org/10.1016/j.micres.2021.126898

Kuhlmann AU, Bremer E (2002) Osmotically regulated synthesis of the compatible solute ectoine in Bacillus pasteurii and related Bacillus spp. Appl Environ Microb 68:772–783. https://doi.org/10.1128/aem.68.2.772-783.2002 DOI

Lang YJ, Bai L, Ren YN, Zhang LH, Nagata S (2011) Production of ectoine through a combined process that uses both growing and resting cells of Halomonas salina DSM 5928 DOI

Lee J, Ozcan U (2014) Unfolded protein response signaling and metabolic diseases. J Biol Chem 289:1203–1211. https://doi.org/10.1074/jbc.R113.534743 DOI

León MJ, Hoffmann T, Sánchez-Porro C, Heider J, Ventosa A, Bremer E (2018) Compatible solute synthesis and import by the moderate halophile Spiribacter salinus: Physiology and genomics. Front Microbiol 9:108. https://doi.org/10.3389/fmicb.2018.00108 DOI

Li TT, Qu A, Yuan XN, Tan FX, Li XW, Wang T, Zhang LH (2017) Response surface method optimization of ectoine fermentation medium with moderate halophilic bacteria Halomonas sp. H02. IOP Conference Series: Earth Env Sci 77:012019. https://doi.org/10.1088/1755-1315/77/1/012019

Meyer S, Schroeter MA, Hahn MB, Solomun T, Sturm H, Kunte HJ (2017) Ectoine can enhance structural changes in DNA in vitro. Sci Rep 7:7170. https://doi.org/10.1038/s41598-017-07441-z DOI

Müller D, Lindemann T, Shah-Hosseini K, Scherner O, Knop M, Bilstein A, Mosges R (2016) Efficacy and tolerability of an ectoine mouth and throat spray compared with those of saline lozenges in the treatment of acute pharyngitis and/or laryngitis: a prospective, controlled, observational clinical trial. Eur Arch Oto-Rhino-Laryngol 273:2591–2597. https://doi.org/10.1007/s00405-016-4060-z DOI

Mustakhimov II, Reshetnikov AS, Glukhov AS, Khmelenina VN, Kalyuzhnaya MG, Trotsenko YA (2010a) Identification and characterization of EctR1, a new transcriptional regulator of the ectoine biosynthesis genes in the halotolerant methanotroph Methylomicrobium alcaliphilum 20Z. J Bacteriol 192:410–417. https://doi.org/10.1128/Jb.00553-09 DOI

Mustakhimov II, Reshetnikov AS, Khmelenina VN, Trotsenko YA (2010b) Regulatory aspects of ectoine biosynthesis in halophilic bacteria. Microbiology 79:583–592. https://doi.org/10.1134/s0026261710050024 DOI

Ning YK, Wu XJ, Zhang CL, Xu QY, Chen N, Xie XX (2016) Pathway construction and metabolic engineering for fermentative production of ectoine in Escherichia coli. Metab Eng 36:10–18. https://doi.org/10.1016/j.ymben.2016.02.013 DOI

Ofer N, Wishkautzan M, Meijler MM, Wang Y, Speer A, Niederweis M, Gur E (2012) Ectoine biosynthesis in Mycobacterium smegmatis. Appl Environ Microb 78:7483–7486. https://doi.org/10.1128/aem.01318-12 DOI

Oren A, Heldal M, Norland S, Galinski EA (2002) Intracellular ion and organic solute concentrations of the extremely halophilic bacterium Salinibacter ruber. Extremophiles 6:491–498. https://doi.org/10.1007/s00792-002-0286-3 DOI

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. https://doi.org/10.1016/j.biotechadv.2010.06.005 DOI

Rajan LA, Joseph TC, Thampuran N, James R (2010) Functional characterization, secondary structure prediction and analysis of ectoine biosynthesis genes from Bacillus halodurans: an osmolyte involved in stress tolerance. World J Microb Biot 26:2093–2098. https://doi.org/10.1007/s11274-010-0379-6 DOI

Refaat R, Sarhan D, Kotb M, El-Abd E, El-Bassiouni E (2018) Post-irradiation protective effects of ectoine on brain and testicles in male mice. Pharmacol Rep 70:304–308. https://doi.org/10.1016/j.pharep.2017.10.002 DOI

Roberts MF (2004) Osmoadaptation and osmoregulation in archaea: Update 2004. Front Biosci 9:1999–2019. https://doi.org/10.2741/1366 DOI

Rohles CM, Giesselmann G, Kohlstedt M, Wittmann C, Becker J (2016) Systems metabolic engineering of Corynebacterium glutamicum for the production of the carbon-5 platform chemicals 5-aminovalerate and glutarate. Microb Cell Fact 15:154. https://doi.org/10.1186/s12934-016-0553-0 DOI

Salmannejad F, Nafissi-Varcheh N (2017) Ectoine and hydroxyectoine inhibit thermal-induced aggregation and increase thermostability of recombinant human interferon Alfa2b. Eur J Pharm Sci 97:200–207. https://doi.org/10.1016/j.ejps.2016.11.014 DOI

Sarhan DA, Shehata RR, Kandil YI, Kotb MA, El-Bassiouni EA (2016) Influence of whole body X-irradiation on the liver and possible protective effect by the compatible solute ectoine in a mouse model. Eur J Biophysics 4:16–21. https://doi.org/10.11648/j.ejb.20160403.11

Sauer T, Galinski EA (1998) Bacterial milking: a novel bioprocess for production of compatible solutes. Biotechnol Bioeng 57:306–313. https://doi.org/10.1002/(sici)1097-0290(19980205)57:3%3c306::aid-bit7%3e3.0.co;2-l DOI

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. https://doi.org/10.1038/s41598-017-15512-4 DOI

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 2581 T. Environ Microbiol 13:1973–1994. https://doi.org/10.1111/j.1462-2920.2010.02336.x DOI

Stiller LM, Galinski EA, Witt EMHJ (2018) Engineering the salt-inducible ectoine promoter region of Halomonas elongata for protein expression in a unique stabilizing environment. Genes 9:184. https://doi.org/10.3390/genes9040184 DOI

Stoveken N, Pittelkow M, Sinner T, Jensen RA, Heider J, Bremer E (2011) A specialized aspartokinase enhances the biosynthesis of the osmoprotectants ectoine and hydroxyectoine in Pseudomonas stutzeri A1501. J Bacteriol 193:4456–4468. https://doi.org/10.1128/JB.00345-11 DOI

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. https://doi.org/10.1183/09031936.00132211 DOI

Tanimura K, Matsumoto T, Nakayama H, Tanaka T, Kondo A (2016) Improvement of ectoine productivity by using sugar transporter-overexpressing Halomonas elongata. Enzyme Microb Technol 89:63–68. https://doi.org/10.1016/j.enzmictec.2016.03.006 DOI

Tao P, Li H, Yu YJ, Gu JD, Liu YD (2016) Ectoine and 5-hydroxyectoine accumulation in the halophile Virgibacillus halodenitrificans PDB-F2 in response to salt stress. Appl Microbiol Biot 100:6779–6789. https://doi.org/10.1007/s00253-016-7549-x DOI

Tuncer Budanur D, Zibandeh N, Genc D, Gokalp M, Kasali K, Akkoc T, Sepet E (2018) Effect of cDMEM media containing ectoine on human periodontal ligament mesenchymal stem cell survival and differentiation. Dent Traumatol 34:188–200. https://doi.org/10.1111/edt.12396 DOI

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. https://doi.org/10.1155/2014/708458 DOI

Unfried K, Kramer U, Sydlik U, Autengruber A, Bilstein A, Stolz S, Marini A, Schikowski T, Keymel S, Krutmann J (2016) Reduction of neutrophilic lung inflammation by inhalation of the compatible solute ectoine: a randomized trial with elderly individuals. Int J Chronic Obstr 11:2573–2583. https://doi.org/10.2147/COPD.S115061 DOI

Wei YH, Yuan FW, Chen WC, Chen SY (2011) Production and characterization of ectoine by Marinococcus sp. ECT1 isolated from a high-salinity environment. J Biosci Bioeng 111:336–342. https://doi.org/10.1016/j.jbiosc.2010.11.009 DOI

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. https://doi.org/10.1155/2014/176597 DOI

Widderich N, Kobus S, Hoppner A, Riclea R, Seubert A, Dickschat JS, Heider J, Smits SH, Bremer E (2016) Biochemistry and crystal structure of ectoine synthase: a metal-containing member of the cupin superfamily. PLoS ONE 11:e0151285. https://doi.org/10.1371/journal.pone.0151285 DOI

Yao CL, Lin YM, Mohamed MS, Chen JH (2013) Inhibitory effect of ectoine on melanogenesis in B16–F0 and A2058 melanoma cell lines. Biochem Eng J 78:163–169. https://doi.org/10.1016/j.bej.2013.01.005 DOI

Zhang Lh, Yj L, Nagata S (2009) Efficient production of ectoine using ectoine-excreting strain. Extremophiles 13:717–724. https://doi.org/10.1007/s00792-009-0262-2 DOI

Zhang LH, Zheng X, Lang YJ (2011) Metabolic flux analysis and optimal control in the process of ectoine fermentation. Adv Mat Res 393–395:851–854. https://doi.org/10.4028/www.scientific.net/AMR.393-395.851 DOI

Zhang T, Cui T, Cao Y, Li Y, Li F, Zhu D, Xing J (2022) Whole genome sequencing of the halophilic Halomonas qaidamensis XH36, a novel species strain with high ectoine production. Antonie Van Leeuwenhoek, Int J Gen Mol Microbiol 115:545–559. https://doi.org/10.1007/s10482-022-01709-9 DOI

Zhou Y, Sun ZY, Li H, Qian CJ, Wu X, Tang HZ, Ali F, Liu YD (2017) Investigation of compatible solutes synthesis and transport of Virgibacillus halodenitrificans PDB-F2 with complete genome analysis. Int Biodeter Biodegr 122:165–172. https://doi.org/10.1016/j.ibiod.2017.05.005 DOI

Zhu D, Niu L, Wang C, Nagata S (2007) Isolation and characterisation of moderately halophilic bacterium Halomonas ventosae DL7 synthesizing ectoine as compatible solute. Ann Microbiol 57:401–406. https://doi.org/10.1007/bf03175080 DOI

Zhu DR, Liu J, Han R, Shen GP, Long QF, Wei XX, Liu DL (2014) Identification and characterization of ectoine biosynthesis genes and heterologous expression of the ectABC gene cluster from Halomonas sp. QHL1, a moderately halophilic bacterium isolated from qinghai lake. J Microbiol 52:139–147. https://doi.org/10.1007/s12275-014-3389-5 DOI