Applied Microbiology and Biotechnology

, Volume 102, Issue 21, pp 9331–9350 | Cite as

The ethanol-induced global alteration in Arthrobacter simplex and its mutants with enhanced ethanol tolerance

  • Jianmei LuoEmail author
  • Zhaoyu Song
  • Jing Ning
  • Yongxin Cheng
  • Yanxia Wang
  • Fangfang Cui
  • Yanbing Shen
  • Min Wang
Applied microbial and cell physiology


Arthrobacter simplex has received considerable interests due to its superior Δ1-dehydrogenation ability. Ethanol used as co-solvent is a stress commonly encountered during biotransformation. Therefore, studies of ethanol tolerance of A. simplex are of great importance to improve the biotransformation efficiency. In this paper, the combined analysis of physiological properties, cell compositions, stress-responsive metabolites, and proteome profiles was carried out to achieve a global view of ethanol tolerance of A. simplex. Under sublethal conditions, cell permeability and membrane fluidity exhibited concentration-dependent increase by affecting the contents or compositions of cell peptidoglycan, lipids, phospholipids, and fatty acids. Among them, cistrans isomerization of unsaturated fatty acids was a short-term and reversible process, while the changes in phospholipid headgroups and increase in saturation degree of fatty acids were long-term and irreversible processes, which collectively counteracted the elevated membrane fluidity caused by ethanol and maintained the membrane stability. The decreased intracellular ATP content was observed at high ethanol concentration since proton motive force responsible for driving ATP synthesis was dissipated. The involvement of trehalose and glycerol, oxidative response, and DNA damage were implicated due to their changes in positive proportion to ethanol concentration. Proteomic data supported that ethanol invoked a global alteration, among which, the change patterns of proteins participated in the biosynthesis of cell wall and membrane, energy metabolism, compatible solute metabolism, and general stress response were consistent with observations from cell compositions and stress-responsive metabolites. The protective role of proteins participated in DNA repair and antioxidant system under ethanol stress was validated by overexpression of the related genes. This is the first demonstration on ethanol tolerance mechanism of A. simplex, and the current studies also provide targets to engineer ethanol tolerance of A. simplex.


Ethanol response Physiological property Cell composition Proteome Arthrobacter simplex Steroid transformation 


Funding information

This work was financially supported by Natural Science Foundation of China (nos. 21306138 and 21646017), the Natural Science Foundation of Tianjin (nos. 18JCZDJC32500), and Tianjin Municipal Science and Technology Commission (17PTGCCX00190).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2018_9301_MOESM1_ESM.pdf (747 kb)
ESM 1 (PDF 746 kb)


  1. Alexandre H, Plourde L, Charpentier C, Francois J (1998) Lack of correlation between trehalose accumulation, cell viability and intracellular acidification as induced by various stresses in Saccharomyces cerevisiae. Microbiology 144(4):1103–1111. CrossRefPubMedGoogle Scholar
  2. Alsaker KV, Paredes C, Papoutsakis ET (2010) Metabolite stress and tolerance in the production of biofuels and chemicals: gene-expression-based systems analysis of butanol, butyrate and acetate stresses in the anaerobe Clostridium acetobutylicum. Biotechnol Bioeng 105(6):1131–1147. CrossRefPubMedGoogle Scholar
  3. Alsaker KV, Spitzer TR, Papoutsakis ET (2004) Transcriptional analysis of spo0A overexpression in Clostridium acetobutylicum and its effect on the cell’s response to butanol stress. J Bacteriol 186(7):1959–1971. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bansal VS, Khuller GK (1981) Changes in phospholipids of Microsporum species in the presence of ethanol. Arch Microbiol 130(3):248–249. CrossRefGoogle Scholar
  5. Beaven MJ, Charpentier C, Rose AH (1982) Production and tolerance of ethanol in relation to phospholipid fatty-acyl composition in Saccharomyces cerevisiae NCYC 431. J Gen Microbiol 128(7):1447–1455Google Scholar
  6. Bowles LK, Ellefson WL (1985) Effects of butanol on Clostridium acetobutylicum. Appl Environ Microbiol 50(5):1165–1170PubMedPubMedCentralGoogle Scholar
  7. Budin-Verneuil A, Pichereau V, Auffray Y, Ehrlich DS, Maguin E (2005) Proteomic characterization of the acid tolerance response in Lactococcus lactis MG1363. Proteomics 5(18):4794–4807. CrossRefPubMedGoogle Scholar
  8. Carey VC, Ingram LO (1983) Lipid composition of Zymomonas mobilis: effects of ethanol and glucose. J Bacteriol 154(3):1291–1300PubMedPubMedCentralGoogle Scholar
  9. Chen TJ, Wang JQ, Zeng LL, Li RZ, Li GC, Chen YL, Lin ZN (2012) Significant rewiring of the transcriptome and proteome of an Escherichia coli strain harboring a tailored exogenous global regulator IrrE. PLoS One 7(7):e37126. CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chiou RYY, Phillips RD, Zhao P, Doyle MP, Beuchat LR (2004) Ethanol-mediated variations in cellular fatty acid composition and protein profiles of two genotypically different strains of Escherichia coli O157:H7. Appl Environ Microbiol 70(4):2204–2210. CrossRefPubMedPubMedCentralGoogle Scholar
  11. de Carvalho CCCR, Parreno-Marchante B, Neumann G, da Fonseca MMR, Heipieper HJ (2005) Adaptation of Rhodococcus erythropolis DCL14 to growth on n-alkanes, alcohols and terpenes. Appl Microbiol Biotechnol 67(3):383–388. CrossRefPubMedGoogle Scholar
  12. Devantier R, Scheithauer B, Villas-Boas SG, Pedersen S, Olsson L (2005) Metabolite profiling for analysis of yeast stress response during very high gravity ethanol fermentations. Biotechnol Bioeng 90(6):703–714. CrossRefPubMedGoogle Scholar
  13. Ding J, Huang X, Zhang L, Zhao N, Yang D, Zhang K (2009) Tolerance and stress response to ethanol in the yeast Saccharomyces cerevisiae. Appl Microbiol Biotechnol 85(2):253–263CrossRefGoogle Scholar
  14. Dominique ML, Bruno L (2005) Structure and metabolism of peptidoglycan and molecular requirements allowing its detection by the Drosophila innate immune system. J Endotoxin Res 11(2):105–111. CrossRefGoogle Scholar
  15. Duldhardt I, Nijenhuis I, Schauer F, Heipieper HJ (2007) Anaerobically grown Thauera aromatica, Desulfococcus multivorans, Geobacter sulfurreducens are more sensitive towards organic solvents than aerobic bacteria. Appl Microbiol Biotechnol 77(3):705–711. CrossRefPubMedGoogle Scholar
  16. Franck P, Petitipain N, Cherlet M, Dardennes M, Maachi F, Schutz B, Poisson L, Nabet P (1996) Measurement of intracellular pH in cultured cells by flow cytometry with BCECF-AM. J Biotechnol 46(3):187–195. CrossRefPubMedGoogle Scholar
  17. Fu FF, Cheng VWT, Wu YM, Tang YN, Weiner JH, Li L (2013) Comparative proteomic and metabolomic analysis of Staphylococcus warneri SG1 cultured in the presence and absence of butanol. J Proteome Res 12(10):4478–4489. CrossRefPubMedGoogle Scholar
  18. Gomes FCO, Pataro C, Guerra JB, Neves MJ, Correa SR, Moreira ESA, Rosa CA (2002) Physiological diversity and trehalose accumulation in Schizosaccharomyces pombe strains isolated from spontaneous fermentation during the production of Brazilian cachaça. Can J Microbiol 48(5):399–406. CrossRefGoogle Scholar
  19. Gonzalez R, Tao H, Purvis JE, York SW, Shanmugam KT, Ingram LO (2003) Gene array-based identification of changes that contribute to ethanol tolerance in ethanologenic Escherichia coli: comparison of KO11 (parent) to LY01 (resistant mutant). Biotechnol Prog 19(2):612–623. CrossRefPubMedGoogle Scholar
  20. Goodarzi H, Bennett BD, Amini S, Reaves ML, Hottes AK, Rabinowitz JD, Tavazoie S (2010) Regulatory and metabolic rewiring during laboratory evolution of ethanol tolerance in E. coli. Mol Syst Biol 6:378. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gulston M, Lara CD, Jenner T, Davis E, O’Neill P (2004) Processing of clustered DNA damage generates additional double-strand breaks in mammalian cells post-irradiation. Nucleic Acids Res 32(4):1602–1609. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Gunasekera TS, Csonka LN, Paliy O (2008) Genome-wide transcriptional responses of Escherichia coli K-12 to continuous osmotic and heat stresses. J Bacteriol 190(10):3712–3720. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Heipieper HJ, Diefenbach R, Keweloh H (1992) Conversion of cis unsaturated fatty acids to trans, a possible mechanism for the protection of phenol-degrading Pseudomonas putida P8 from substrate toxicity. Appl Environ Microbiol 58(6):1847–1852PubMedPubMedCentralGoogle Scholar
  24. Heipieper HJ, Meinhardt F, Segura A (2003) The cis-trans isomerase of unsaturated fatty acids in Pseudomonas and Vibrio: biochemistry, molecular biology and physiological function of a unique stress adaptive mechanism. FEMS Microbiol Lett 229(1):1–7. CrossRefPubMedGoogle Scholar
  25. Herrero AA, Gomez RF, Roberts MF (1982) Ethanol-induced changes in the membrane lipid composition of Clostridium thermocellum. Biochim Biophys Acta 693(1):195–204. CrossRefPubMedGoogle Scholar
  26. Ingram LO (1976) Adaptation of membrane lipids to alcohols. J Bacteriol 125(2):670–678PubMedPubMedCentralGoogle Scholar
  27. Ingram LO (1977) Changes in lipid composition of Escherichia coli resulting from growth with organic solvents and with food additives. Appl Environ Microbiol 33(5):1233–1236PubMedPubMedCentralGoogle Scholar
  28. Ingram LO, Vreeland NS, Eaton LC (1980) Alcohol tolerance in Escherichia coli. Pharmacol Biochem Behav 13(s1–2):191–195. CrossRefPubMedGoogle Scholar
  29. Janssen H, Grimmler C, Ehrenreich A, Bahla H, Fischer RJ (2012) A transcriptional study of acidogenic chemostat cells of Clostridium acetobutylicum-solvent stress caused by a transient n-butanol pulse. J Bacteriol 161:354–365. CrossRefGoogle Scholar
  30. Kabelitz N, Santos PM, Heipieper HJ (2003) Effect of aliphatic alcohols on growth and degree of saturation of membrane lipids in Acinetobacter calcoaceticus. FEMS Microbiol Lett 220(2):223–227. CrossRefPubMedGoogle Scholar
  31. Kaino T, Takagi H (2008) Gene expression profiles and intracellular contents of stress protectants in Saccharomyces cerevisiae under ethanol and sorbitol stresses. Appl Microbiol Biotechnol 79(2):273–283. CrossRefPubMedGoogle Scholar
  32. Kandror DeLeon A, Goldberg AL (2002) Trehalose synthesis is induced upon exposure of Escherichia coli to cold and is essential for viability at low temperatures. Proc Natl Acad Sci U S A 99(15):9727–9732. CrossRefPubMedGoogle Scholar
  33. Kang YS, Lee L, Jung H, Jeon CO, Madsen EL, Park W (2007) Overexpressing antioxidant enzymes enhances naphthalene biodegradation in Pseudomonas sp. strain As1. Microbiology 153(10):3246–3254. CrossRefPubMedGoogle Scholar
  34. Kempf Bremer E (1998) Uptake and synthesis of compatible solutes as microbial stress responses to high-osmolality environments. Arch Microbiol 170(5):319–330. CrossRefPubMedGoogle Scholar
  35. Leao C, Van Uden N (1984) Effects of ethanol and other alkanols on passive proton influx in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 774(1):43–48. CrossRefPubMedGoogle Scholar
  36. Lepage C, Fayolle F, Hermann M, Vandecasteele JP (1987) Changes in membrane lipid composition of Clostridium acetobutylicum during acetone-butanol fermentation: effects of solvents, growth temperature and pH. J Gen Microbiol 133(1):103–110. CrossRefGoogle Scholar
  37. Luo JM, Ning J, Wang YX, Cheng YX, Zheng Y, Shen YB, Wang M (2013) The effect of ethanol on cell properties and steroid 1-en-dehydrogenation biotransformation of Arthrobacter simplex. Biotechnol Appl Biochem 61(5):555–564. CrossRefGoogle Scholar
  38. Mahipant G, Paemanee A, Roytrakul S, Kato J, Vangna AS (2017) The significance of proline and glutamate on butanol chaotropic stress in Bacillus subtilis 168. Biotechnol Biofuels 10:122–136. CrossRefPubMedPubMedCentralGoogle Scholar
  39. Mao S, Luo Y, Bao G, Zhang Y, Li Y, Ma Y (2011) Comparative analysis on the membrane proteome of Clostridium acetobutylicum wild type strain and its butanol-tolerant mutant. Mol BioSyst 7(5):1660–1677. CrossRefPubMedGoogle Scholar
  40. Marks VD, Ho Sui SJ, Erasmus D, van der Merwe GK, Brumm J, Wasserman WW, Bryan J, van Vuuren HJ (2008) Dynamics of the yeast transcriptome during wine fermentation reveals a novel fermentation stress response. FEMS Yeast Res 8(1):35–52. CrossRefPubMedPubMedCentralGoogle Scholar
  41. Marrakchi H, Zhang YM, Rock CO (2002) Mechanistic diversity and regulation of type II fatty acid synthesis. Biochem Soc 730:1050–1055. CrossRefGoogle Scholar
  42. Matallana-Surget S, Joux F, Wattiez R, Lebaron P (2012) Proteome analysis of the UVB-resistant marine bacterium Photobacterium angustum S14. PLoS One 7(8):e42299. CrossRefPubMedPubMedCentralGoogle Scholar
  43. Miller EN, Ingram LO (2008) Sucrose and overexpression of trehalose biosynthetic genes (otsBA) increase desiccation tolerance of recombinant Escherichia coli. Biotechnol Lett 30(3):503–508. CrossRefPubMedGoogle Scholar
  44. Mykytczuk NCS, Trevors JT, Leduc LG, Ferroni GD (2007) Fluorescence polarization in studies of bacterial cytoplasmic membrane fluidity under environmental stress. Prog Biophys Mol Biol 95:60–82. CrossRefPubMedGoogle Scholar
  45. Narumi I, Satoh K, Kikuchi M, Funayama T, Kitayama S, Yanagisawa T, Watanabe H, Yamamoto K (1999) Molecular analysis of the Deinococcus radiodurans recA locus and identification of a mutation site in a DNA repair-deficient mutant. Mutat Res 435(3):233–243. CrossRefPubMedGoogle Scholar
  46. Nielsen LE, Kadavy DR, Rajagopal S, Drijber R, Nickerson KW (2005) Survey of extreme solvent tolerance in Gram-positive cocci: membrane fatty acid changes in Staphylococcus haemolyticus grown in toluene. Appl Environ Microbiol 71(9):5171–5176. CrossRefPubMedPubMedCentralGoogle Scholar
  47. Ogawa Y, Nitta A, Uchiyama H, Imamura T, Shimoi H, Ito K (2000) Tolerance mechanism of the ethanol-tolerant mutant of sake yeast. J Biosci Bioeng 90(3):313–320. CrossRefPubMedGoogle Scholar
  48. Pepi M, Heipieper HJ, Fischer J, Ruta M, Volterrani M, Focardi SE (2008) Membrane fatty acids adaptive profile in the simultaneous presence of arsenic and toluene in Bacillus sp. ORAs2 and Pseudomonas sp. ORAs5 strains. Extremophiles 12(3):343–349. CrossRefPubMedGoogle Scholar
  49. Pinkart HC, White DC (1997) Phospholipid biosynthesis and solvent tolerance in Pseudomonas putida strains. J Bacteriol 179(13):4219–4226. CrossRefPubMedPubMedCentralGoogle Scholar
  50. Rigomier D, Bohin JP, Lubochinsky B (1980) Effects of ethanol and methanol on lipid metabolism in Bacillus subtilis. J Gen Microbiol 121(1):139–149PubMedGoogle Scholar
  51. Royce LA, Yoon JM, Chen YX, Rickenbach E, Shanks JV, Jarboe LR (2015) Evolution for exogenous octanoic acid tolerance improves carboxylic acid production and membrane integrity. Metab Eng 29:180–188. CrossRefPubMedGoogle Scholar
  52. Rutherford BJ, Dahl RH, Price RE, Szmidt HL, Benke PI, Mukhopadhyay A, Keasling JD (2010) Functional genomic study of exogenous n-butanol stress in Escherichia coli. Appl Environ Microbiol 76(6):1935–1945. CrossRefPubMedPubMedCentralGoogle Scholar
  53. Sandu C, Chiribau CB, Sachelaru P, Brandsch R (2005) Plasmids for nicotine-dependent and -independent gene expression in Arthrobacter nicotinovorans and other Arthrobacter species. Appl Environ Microbiol 71(12):8920–8924. CrossRefPubMedPubMedCentralGoogle Scholar
  54. Sandoval NR, Papoutsakis ET (2016) Engineering membrane and cell-wall programs for tolerance to toxic chemicals: beyond solo genes. Curr Opin Microbiol 33:56–66. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Segura A, Molina L, Fillet S, Krell T, Bernal P, Munoz-Rojas J, Ramos JL (2012) Solvent tolerance in Gram-negative bacteria. Curr Opin Biotechnol 23(3):415–421. CrossRefPubMedGoogle Scholar
  56. Shah AA, Wang CL, Yoon SH, Kim JY, Choi ES, Kim SW (2013) RecA-mediated SOS response provides a geraniol tolerance in Escherichia coli. J Biotechnol 167(4):357–364. CrossRefPubMedGoogle Scholar
  57. Shen YB, Wang M, Zhang LT, Ma YH, Ma B, Zheng Y, Liu H, Luo JM (2011) Effects of hydroxypropyl-β-cyclodextrin on cell growth, activity, and integrity of steroid-transforming Arthrobacter simplex and Mycobacterium sp. Appl Microbiol Biotechnol 90(6):1995–2003. CrossRefPubMedGoogle Scholar
  58. Shen YB, Liang JT, Li H, Wang M (2014) Hydroxypropyl-β-cyclodextrin-mediated alterations in cell permeability, lipid and protein profiles of steroid-transforming Arthrobacter simplex. Appl Microbiol Biotechnol 99(1):387–397. CrossRefPubMedGoogle Scholar
  59. Shimizu K, Hayashi S, Kako T, Suzuki M, Tsukagoshi N, Doukyu N, Kobayashi T, Honda H (2005) Discovery of glpC, an organic solvent tolerance-related gene in Escherichia coli, using gene expression profiles from DNA microarrays. Appl Environ Microbiol 71(2):1093–1096. CrossRefPubMedPubMedCentralGoogle Scholar
  60. Takahashi T, Shimoi H, Ito K (2001) Identification of genes required for growth under ethanol stress using transposon mutagenesis in Saccharomyces cerevisiae. Mol Gen Genomics 265(6):1112–1119CrossRefGoogle Scholar
  61. Taneja R, Khuller GK (1980) Ethanol-induced alterations in phopholipids and fatty acids of Mycobacterium smegmatis ATCC 607. FEMS Microbiol Lett 8(2):83–85CrossRefGoogle Scholar
  62. Terracciano JS, Rapaport E, Kashket ER (1988) Stress phase-associated and growth phase-associated proteins of Clostridium acetobutylicum. Appl Environ Microbiol 54(8):1989–1995PubMedPubMedCentralGoogle Scholar
  63. Tian B, Guan Z, Goldfine H (2013) An ethanolamine-phosphate modified glycolipid in Clostridium acetobutylicum that responds to membrane stress. Biochim Biophys Acta 1831(6):1185–1190. CrossRefPubMedPubMedCentralGoogle Scholar
  64. Tomas CA, Beamish J, Papoutsakis ET (2004) Transcriptional analysis of butanol stress and tolerance in Clostridium acetobutylicum. J Bacteriol 186(7):2006-2018. CrossRefPubMedPubMedCentralGoogle Scholar
  65. Tomas CA, Welker NE, Papoutsakis ET (2003) Overexpression of groESL in Clostridium acetobutylicum results in increased solvent production and tolerance, prolonged metabolism, and changes in the cell’s transcriptional program. Appl Environ Microbiol 69(8):4951–4965. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Torres S, Pandey A, Castro GR (2011) Organic solvent adaptation of Gram positive bacteria: application and biotechnological potentials. Biotechnol Adv 29(4):442–452. CrossRefPubMedGoogle Scholar
  67. Uchida K (1975) Effects of cultural conditions on the cellular fatty acid composition of Lactobacillus heterohiochii, an alcoholophilic bacterium. Agric Biol Chem 39(4):837–842. CrossRefGoogle Scholar
  68. Unell M, Kabelitz N, Jansson JK, Heipieper HJ (2007) Adaptation of the psychrotroph Arthrobacter chlorophenolicus A6 to growth temperature and the presence of phenols by changes in the anteiso/iso ratio of branched fatty acids. FEMS Microbiol Lett 266(2):138–143. CrossRefPubMedGoogle Scholar
  69. Venkataramanan KP, Lie M, Hou SY, Jones SW, Ralston MT, Lee KH, Papoutsakis ET (2015) Complex and extensive post-transcriptional regulation revealed by integrative proteomic and transcriptomic analysis of metabolite stress response in Clostridium acetobutylicum. Biotechnol Biofuels 81(8):81. CrossRefGoogle Scholar
  70. Vianna CR, Silva CL, Neves MJ, Rosa CA (2008) Saccharomyces cerevisiae strains from traditional fermentations of Brazilian cachaça: trehalose metabolism, heat and ethanol resistance. Antonie Van Leeuwenhoek 93:205–217CrossRefGoogle Scholar
  71. Volkers RJ, Ballerstedt H, Ruijssenaars H, de Bont JA, de Winde JH, Wery J (2009) TrgI, toluene repressed gene I, a novel gene involved in toluene-tolerance in Pseudomonas putida S12. Extremophiles 13(2):283–297. CrossRefPubMedGoogle Scholar
  72. Volkers RJM, de Jong AL, Hulst AG, van Baar BLM, de Bont JAM, Wery J (2006) Chemostat-based proteomic analysis of toluene-affected Pseudomonas putida S12. Environ Microbiol 8(9):1674–1679. CrossRefPubMedGoogle Scholar
  73. Wang FQ, Kashket S, Kashket ER (2005) Maintenance of Delta pH by a butanol-tolerant mutant of Clostridium beijerinckii. Microbiology 151(2):607–613. CrossRefPubMedGoogle Scholar
  74. Weber FJ, de Bont JAM (1996) Adaptation mechanisms of microorganisms to the toxic effects of organic solvents on membranes. Biochim Biophys Acta 1286(3):225–245. CrossRefPubMedGoogle Scholar
  75. Wijte D, van Baar BL, Heck AJ, Altelaar AF (2011) Probing the proteome response to toluene exposure in the solvent tolerant Pseudomonas putida S12. J Proteome Res 10(2):394–403. CrossRefPubMedGoogle Scholar
  76. Wu CD, Zhang J, Chen W, Wang M, Du JC, Chen J (2012) A combined physiological and proteomic approach to reveal lactic-acid-induced alterations in Lactobacillus casei Zhang and its mutant with enhanced lactic acid tolerance. Appl Microbiol Biotechnol 93(2):707–722. CrossRefPubMedGoogle Scholar
  77. Wu H, Zheng X, Araki Y, Sahara H, Takagi H, Shimoi H (2006) Global gene expression analysis of yeast cells during sake brewing. Appl Environ Microbiol 72(11):7353–7735. CrossRefPubMedPubMedCentralGoogle Scholar
  78. You KM, Rosenfield CL, Knipple DC (2003) Ethanol tolerance in the yeast Saccharomyces cerevisiae is dependent on cellular oleic acid content. Appl Environ Microbiol 69(3):1499–1503. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jianmei Luo
    • 1
    • 2
    Email author
  • Zhaoyu Song
    • 1
  • Jing Ning
    • 1
  • Yongxin Cheng
    • 1
  • Yanxia Wang
    • 1
  • Fangfang Cui
    • 1
  • Yanbing Shen
    • 1
  • Min Wang
    • 1
  1. 1.Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin Key Lab of Industrial Microbiology, Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, College of BiotechnologyTianjin University of Science and TechnologyTianjinPeople’s Republic of China
  2. 2.Tianjin Economic-Technological Development Area (TEDA)TianjinPeople’s Republic of China

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