Microbial mutagenesis by atmospheric and room-temperature plasma (ARTP): the latest development

Abstract

Although rational genetic engineering is nowadays the favored method for microbial strain improvement, random mutagenesis is still in many cases the only option. Atmospheric and room-temperature plasma (ARTP) is a newly developed whole-cell mutagenesis tool based on radio-frequency atmospheric-pressure glow discharge plasma which features higher mutation rates than UV radiation or chemical mutagens while maintaining low treatment temperatures. It has been successfully applied on at least 24 bacterial and 14 fungal species, but also on plants, dinoflagellates, and other microbial communities for the improvement of tolerance to medium components, to increase cellular growth and production of cellular biomass, to enhance enzyme activity, and to increase the production of various chemicals. Achievements like 385.7% of acetic acid production enhancement in Acetobacter pasteurianus give this new mutagenesis tool a promising future. However, certain questions remain regarding optimal operational conditions, the effects at subcellular levels, and standard operation procedures, which need to be addressed to facilitate applications of ARTP in microbial breeding and other fields such as evolution of enzymes.

Keywords

Random mutagenesis / Atmospheric and room-temperature plasma / Mutation mechanism / Strain breeding / Industrial application

References

[1] An J, Gao F, Ma Q, Xiang Y, Ren D, Lu J. Screening for enhanced astaxanthin accumulation among Spirulina platensis mutants generated by atmospheric and room temperature plasmas. Algal Res, 2017, 25: 464-472.

[2] Arjunan K, Sharma V, Ptasinska S. Effects of atmospheric pressure plasmas on isolated and cellular DNA—a review. Int J Mol Sci, 2015, 16: 2971-3016.

[3] Bao H, Liu R, Liang L, Jiang Y, Jiang M, Ma J, Chen K, Jia H, Wei P, Ouyang P. Succinic acid production from hemicellulose hydrolysate by an Escherichia coli mutant obtained by atmospheric and room temperature plasma and adaptive evolution. Enzyme Microb Technol, 2014, 66: 10-15.

[4] Barrangou R, Horvath P. A decade of discovery: CRISPR functions and applications. Nat Microbiol, 2017, 2: 17092.

[5] Bogaerts A, Neyts E, Gijbels R, van der Mullen J. Gas discharge plasmas and their applications. Spectrochim Acta Part B At Spectrosc, 2002, 57: 609-658.

[6] Bridges BA (2001) SOS repair. In: Brenner S and Miller JH (eds) Encyclopedia of genetics. Elsevier Science, pp 1853–1855

[7] Cao S, Zhou X, Jin W, Wang F, Tu R, Han S, Chen H, Chen C, Xie GJ, Ma F. Improving of lipid productivity of the oleaginous microalgae Chlorella pyrenoidosa via atmospheric and room temperature plasma (ARTP). Bioresour Technol, 2017, 244: 1400-1406.

[8] Cao X, Luo Z, Zeng W, Xu S, Zhao L, Zhou J. Enhanced avermectin production by Streptomyces avermitilis ATCC 31267 using high-throughput screening aided by fluorescence-activated cell sorting. Appl Microbiol Biotechnol, 2018, 102: 703-712.

[9] Cheng G, Xu J, Xia X, Guo Y, Xu K, Su C, Zhang W. Breeding l-arginine-producing strains by a novel mutagenesis method: atmospheric and room temperature plasma (ARTP). Prep Biochem Biotechnol, 2016, 46: 509-516.

[10] Dong J, Zhao W, Gasmalla MAA, Sun J, Hua X, Zhang W, Han L, Fan Y, Feng Y, Shen Q, Yang R. A novel extracellular cold-active esterase of Pseudomonas sp. TB11 from glacier No. 1: differential induction, purification and characterisation. J Mol Catal B Enzym, 2015, 121: 53-63.

[11] Dong J, Gasmalla MAA, Zhao W, Sun J, Liu W, Wang M, Han L, Yang R. Characterization of a cold-adapted esterase and mutants from a psychotolerant Pseudomonas sp. strain. Biotechnol Appl Biochem, 2017, 64: 686-699.

[12] Dong T-T, Gong J-S, Gu B-C, Zhang Q, Li H, Lu Z-M, Lu M-L, Shi J-S, Xu Z-H. Significantly enhanced substrate tolerance of Pseudomonas putida nitrilase via atmospheric and room temperature plasma and cell immobilization. Bioresour Technol, 2017, 244: 1104-1110.

[13] Ermolaeva SA, Varfolomeev AF, Chernukha MY, Yurov DS, Vasiliev MM, Kaminskaya AA, Moisenovich MM, Romanova JM, Murashev AN, Selezneva II, Shimizu T, Sysolyatina EV, Shaginyan IA, Petrov OF, Mayevsky EI, Fortov VE, Morfill GE, Naroditsky BS, Gintsburg AL. Bactericidal effects of non-thermal argon plasma in vitro, in biofilms and in the animal model of infected wounds. J Med Microbiol, 2011, 60: 75-83.

[14] Fan X, Wu H, Li G, Yuan H, Zhang H, Li Y, Xie X, Chen N. Improvement of uridine production of Bacillus subtilis by atmospheric and room temperature plasma mutagenesis and high-throughput screening. PLoS ONE, 2017, 12: e0176545.

[15] Fang M, Jin L, Zhang C, Tan Y, Jiang P, Ge N, Li Heping, Xing X. Rapid mutation of Spirulina platensis by a new mutagenesis system of atmospheric and room temperature plasmas (ARTP) and generation of a mutant library with diverse phenotypes. PLoS ONE, 2013, 8: e77046.

[16] Gu C, Wang G, Mai S, Wu P, Wu J, Wang G, Liu H, Zhang J. ARTP mutation and genome shuffling of ABE fermentation symbiotic system for improvement of butanol production. Appl Microbiol Biotechnol, 2017, 101: 2189-2199.

[17] Guo T, Tang Y, Xi YL, He AY, Sun BJ, Wu H, Liang DF, Jiang M, Ouyang PK. Clostridium beijerinckii mutant obtained by atmospheric pressure glow discharge producing high proportions of butanol and solvent yields. Biotechnol Lett, 2011, 33: 2379-2383.

[18] Hua X, Wang J, Wu Z, Zhang H, Li H, Xing X, Liu Z. A salt tolerant Enterobacter cloacae mutant for bioaugmentation of petroleum- and salt-contaminated soil. Biochem Eng J, 2010, 49: 201-206.

[19] Jiang M, Wan Q, Liu R, Liang L, Chen X, Wu M, Zhang H, Chen K, Ma J, Wei P, Ouyang P. Succinic acid production from corn stalk hydrolysate in an E. coli mutant generated by atmospheric and room-temperature plasmas and metabolic evolution strategies. J Ind Microbiol Biotechnol, 2014, 41: 115-123.

[20] Jiang T, Qiao H, Zheng Z, Chu Q, Li X, Yong Q, Ouyang J. Lactic acid production from pretreated hydrolysates of corn stover by a newly developed Bacillus coagulans strain. PLoS ONE, 2016, 11: e0149101.

[21] Jiang Y, Shang Y-P, Li H, Zhang C, Pan J, Bai Y-P, Li C-X, Xu J-H. Enhancing transglutaminase production of Streptomyces mobaraensis by iterative mutagenesis breeding with atmospheric and room-temperature plasma (ARTP). Bioresour Bioprocess, 2017, 4: 37.

[22] Kalghatgi S, Kelly CM, Cerchar E, Torabi B, Alekseev O, Fridman A, Friedman G, Azizkhan-Clifford J. Effects of non-thermal plasma on mammalian cells. PLoS ONE, 2011, 6: e16270.

[23] Kim OC, Kim SY, Hwang DH, Oh DB, Kang HA, Kwon O. Development of a genome-wide random mutagenesis system using proofreading-deficient DNA polymerase δ in the methylotrophic yeast Hansenula polymorpha. J Microbiol Biotechnol, 2013, 23: 304-312.

[24] Kitahara Y, Yin T, Zhao X, Wachi M, Du W, Liu D. Isolation of oleaginous yeast (Rhodosporidium toruloides) mutants tolerant of sugarcane bagasse hydrolysate. Biosci Biotechnol Biochem, 2014, 78: 336-342.

[25] Kong X, He A, Zhao J, Wu H, Ma J, Wei C, Jin W, Jiang M. Efficient acetone–butanol–ethanol (ABE) production by a butanol-tolerant mutant of Clostridium beijerinckii in a fermentation–pervaporation coupled process. Biochem Eng J, 2016, 105: 90-96.

[26] Kramer A, Bekeschus S, Matthes R, Bender C, Stope MB, Napp M, Lademann O, Lademann J, Weltmann KD, Schauer F. Cold physical plasmas in the field of hygiene—relevance, significance, and future applications. Plasma Process Polym, 2015, 12: 1410-1422.

[27] Lackmann JW, Bandow JE. Inactivation of microbes and macromolecules by atmospheric-pressure plasma jets. Appl Microbiol Biotechnol, 2014, 98: 6205-6213.

[28] Lackmann J-W, Schneider S, Edengeiser E, Jarzina F, Brinckmann S, Steinborn E, Havenith M, Benedikt J, Bandow JE. Photons and particles emitted from cold atmospheric-pressure plasma inactivate bacteria and biomolecules independently and synergistically. J R Soc Interface, 2013, 10: 20130591.

[29] Leduc M, Guay D, Leask RL, Coulombe S. Cell permeabilization using a non-thermal plasma. New J Phys, 2009, 11: 115021.

[30] Lee K, Paek K-H, Ju W-T, Lee Y. Sterilization of bacteria, yeast, and bacterial endospores by atmospheric-pressure cold plasma using helium and oxygen. J Microbiol Microbiol Soc Korea, 2006, 44: 269-275.

[31] Li G, Li H-P, Wang L-Y, Wang S, Zhao H-X, Sun W-T, Xing X-H, Bao C-Y. Genetic effects of radio-frequency, atmospheric-pressure glow discharges with helium. Appl Phys Lett, 2008, 92: 221504.

[32] Li HP, Wang ZB, Ge N, Le PS, Wu H, Lu Y, Wang LY, Zhang C, Bao CY, Xing XH. Studies on the physical characteristics of the radio-frequency atmospheric-pressure glow discharge plasmas for the genome mutation of Methylosinus trichosporium. IEEE Trans Plasma Sci, 2012, 40: 2853-2860.

[33] Li H, Luo W, Wang Q, Yu X. Direct fermentation of gelatinized cassava starch to acetone, butanol, and ethanol using Clostridium acetobutylicum mutant obtained by atmospheric and room temperature plasma. Appl Biochem Biotechnol, 2014, 172: 3330-3341.

[34] Li X, Liu R, Li J, Chang M, Liu Y, Jin Q, Wang X. Enhanced arachidonic acid production from Mortierella alpina combining atmospheric and room temperature plasma (ARTP) and diethyl sulfate treatments. Bioresour Technol, 2015, 177: 134-140.

[35] Li H, Li T, Zuo H, Xiao S, Guo M, Jiang M, Li Z, Li Y, Zou X. A novel rhodamine-based fluorescent pH probe for high-throughput screening of high-yield polymalic acid strains from random mutant libraries. RSC Adv, 2016, 6: 94756-94762.

[36] Li X, Zheng K, Lai C, Ouyang J, Yong Q. Improved itaconic acid production from undetoxified enzymatic hydrolysate of steam-exploded corn stover using an Aspergillus terreus mutant generated by atmospheric and room temperature plasma. BioResources, 2016, 11: 9047-9058.

[37] Liang MH, Liang YJ, Chai JY, Zhou SS, Jiang JG. Reduction of methanol in brewed wine by the use of atmospheric and room-temperature plasma method and the combination optimization of malt with different adjuncts. J Food Sci, 2014, 79: M2308-M2314.

[38] Liu R, Liang L, Ma J, Ren X, Jiang M, Chen K, Wei P, Ouyang P. An engineering Escherichia coli mutant with high succinic acid production in the defined medium obtained by the atmospheric and room temperature plasma. Process Biochem, 2013, 48: 1603-1609.

[39] Liu Q, Lin J, Wang W, Huang H, Li S. Production of surfactin isoforms by Bacillus subtilis BS-37 and its applicability to enhanced oil recovery under laboratory conditions. Biochem Eng J, 2014, 93: 31-37.

[40] Liu B, Sun Z, Ma X, Yang B, Jiang Y, Wei D, Chen F. Mutation breeding of extracellular polysaccharide-producing microalga Crypthecodinium cohnii by a novel mutagenesis with atmospheric and room temperature plasma. Int J Mol Sci, 2015, 16: 8201-8212.

[41] Liu C, Zhang X, Rao Z, Shao M, Zhang L, Wu D, Xu Z, Li H. Mutation breeding of high 4-androstene-3,17-dione-producing Mycobacterium neoaurum ZADF-4 by atmospheric and room temperature plasma treatment. J Zhejiang Univ Sci B, 2015, 16: 286-295.

[42] Liu J, Guo T, Wang D, Ying H. Clostridium beijerinckii mutant obtained atmospheric pressure glow discharge generates enhanced electricity in a microbial fuel cell. Biotechnol Lett, 2015, 37: 95-100.

[43] Liu J, Guo T, Wang D, Xu J, Ying H. Butanol production by a Clostridium beijerinckii mutant with high ferulic acid tolerance. Biotechnol Appl Biochem, 2016, 63: 727-733.

[44] Liu J, Pei G, Diao J, Chen Z, Liu L, Chen L, Zhang W. Screening and transcriptomic analysis of Crypthecodinium cohnii mutants with high growth and lipid content using the acetyl-CoA carboxylase inhibitor sethoxydim. Appl Microbiol Biotechnol, 2017, 101: 6179-6191.

[45] Liu X, Lv J, Xu J, Xia J, Dai B, Xu X, Xu J. Erythritol production by Yarrowia lipolytica mutant strain M53 generated through atmospheric and room temperature plasma mutagenesis. Food Sci Biotechnol, 2017, 26: 979-986.

[46] Lu Y, Wang L, Ma K, Li G, Zhang C, Zhao H, Lai Q, Li HP, Xing XH. Characteristics of hydrogen production of an Enterobacter aerogenes mutant generated by a new atmospheric and room temperature plasma (ARTP). Biochem Eng J, 2011, 55: 17-22.

[47] Lu H, Patil S, Keener KM, Cullen PJ, Bourke P. Bacterial inactivation by high-voltage atmospheric cold plasma: influence of process parameters and effects on cell leakage and DNA. J Appl Microbiol, 2014, 116: 784-794.

[48] Luo Z, Liu S, Du G, Zhou J, Chen J. Identification of a polysaccharide produced by the pyruvate overproducer Candida glabrata CCTCC M202019. Appl Microbiol Biotechnol, 2017, 101: 4447-4458.

[49] Luo Z, Zeng W, Du G, Liu S, Fang F, Zhou J, Chen J. A high-throughput screening procedure for enhancing pyruvate production in Candida glabrata by random mutagenesis. Bioprocess Biosyst Eng, 2017, 40: 693-701.

[50] Lv X, Song J, Yu B, Liu H, Li C, Zhuang Y, Wang Y. High-throughput system for screening of high l-lactic acid-productivity strains in deep-well microtiter plates. Bioprocess Biosyst Eng, 2016, 39: 1737-1747.

[51] Ma Y, Yang H, Chen X, Sun B, Du G, Zhou Z, Song J, Fan Y, Shen W. Significantly improving the yield of recombinant proteins in Bacillus subtilis by a novel powerful mutagenesis tool (ARTP): alkaline α-amylase as a case study. Protein Expr Purif, 2015, 114: 82-88.

[52] Ma J, Wu M, Zhang C, He A, Kong X, Li G, Wei C, Jiang M. Coupled ARTP and ALE strategy to improve anaerobic cell growth and succinic acid production by Escherichia coli. J Chem Technol Biotechnol, 2016, 91: 711-717.

[53] Ma Y, Shen W, Chen X, Liu L, Zhou Z, Xu F, Yang H. Significantly enhancing recombinant alkaline amylase production in Bacillus subtilis by integration of a novel mutagenesis-screening strategy with systems-level fermentation optimization. J Biol Eng, 2016, 10: 13.

[54] Misra NN, Pankaj SK, Segat A, Ishikawa K. Cold plasma interactions with enzymes in foods and model systems. Trends Food Sci Technol, 2016, 55: 39-47.

[55] O’Connell D, Cox LJ, Hyland WB, McMahon SJ, Reuter S, Graham WG, Gans T, Currell FJ. Cold atmospheric pressure plasma jet interactions with plasmid DNA. Appl Phys Lett, 2011, 98: 43701.

[56] Pompl R, Jamitzky F, Shimizu T, Steffes B, Bunk W, Schmidt H-U, Georgi M, Ramrath K, Stolz W, Stark RW, Urayama T, Fujii S, Morfill GE. The effect of low-temperature plasma on bacteria as observed by repeated AFM imaging. New J Phys, 2009, 11: 115023.

[57] Qi F, Kitahara Y, Wang Z, Zhao X, Du W, Liu D. Novel mutant strains of Rhodosporidium toruloides by plasma mutagenesis approach and their tolerance for inhibitors in lignocellulosic hydrolyzate. J Chem Technol Biotechnol, 2014, 89: 735-742.

[58] Qi F, Zhao X, Kitahara Y, Li T, Ou X, Du W, Liu D, Huang J. Integrative transcriptomic and proteomic analysis of the mutant lignocellulosic hydrolyzate-tolerant Rhodosporidium toruloides. Eng Life Sci, 2017, 17: 249-261.

[59] Qiang W, Ling-ran F, Luo W, Han-guang L, Lin W, Ya Z, Xiao-bin Y. Mutation breeding of lycopene-producing strain Blakeslea trispora by a novel atmospheric and room temperature plasma (ARTP). Appl Biochem Biotechnol, 2014, 174: 452-460.

[60] Qin T, Song P, Wang X, Ji X, Ren L, Huang H. Protoplast mutant selection of Glarea lozoyensis and statistical optimization of medium for pneumocandin B0 yield-up. Biosci Biotechnol Biochem, 2016, 80: 2241-2246.

[61] Ren F, Chen L, Tong Q. Highly improved acarbose production of Actinomyces through the combination of ARTP and penicillin susceptible mutant screening. World J Microbiol Biotechnol, 2017, 33: 16.

[62] Shi F, Tan J, Chu J, Wang Y, Zhuang Y, Zhang S. A qualitative and quantitative high-throughput assay for screening of gluconate high-yield strains by Aspergillus niger. J Microbiol Methods, 2015, 109: 134-139.

[63] Sun J, Wang Y, Wu B, Bai Z, He B. Enhanced production of d -lactic acid by Sporolactobacillus sp. Y2-8 mutant generated by atmospheric and room temperature plasma. Biotechnol Appl Biochem, 2015, 62: 287-292.

[64] Tan Y, Fang M, Jin L, Zhang C, Li H-P, Xing X-H. Culture characteristics of the atmospheric and room temperature plasma-mutated Spirulina platensis mutants in CO₂ aeration culture system for biomass production. J Biosci Bioeng, 2015, 120: 438-443.

[65] Tendero C, Tixier C, Tristant P, Desmaison J, Leprince P. Atmospheric pressure plasmas: a review. Spectrochim Acta Part B At Spectrosc, 2006, 61: 2-30.

[66] Twardowski T, Małyska A. Uninformed and disinformed society and the GMO market. Trends Biotechnol, 2015, 33: 1-3.

[67] Wang L-Y, Huang Z-L, Li G, Zhao H-X, Xing X-H, Sun W-T, Li H-P, Gou Z-X, Bao C-Y. Novel mutation breeding method for Streptomyces avermitilis using an atmospheric pressure glow discharge plasma. J Appl Microbiol, 2010, 108: 851-858.

[68] Wang ZB, Le PS, Ge N, Nie QY, Li HP, Bao CY. One-dimensional modeling on the asymmetric features of a radio-frequency atmospheric helium glow discharge produced using a Co-Axial-type plasma generator. Plasma Chem Plasma Process, 2012, 32: 859-874.

[69] Wang H-Y, Zhang J, Zhang Y-J, Zhang B, Liu C-X, He H-R, Wang X-J, Xiang W-S. Combined application of plasma mutagenesis and gene engineering leads to 5-oxomilbemycins A3/A4 as main components from Streptomyces bingchenggensis. Appl Microbiol Biotechnol, 2014, 98: 9703-9712.

[70] Wang X, Lu M, Wang S, Fang Y, Wang D, Ren W, Zhao G. The atmospheric and room-temperature plasma (ARTP) method on the dextranase activity and structure. Int J Biol Macromol, 2014, 70: 284-291.

[71] Wang L, Chen X, Wu G, Li S, Zeng X, Ren X, Tang L, Mao Z. Improved ε-poly-l-lysine production of Streptomyces sp. FEEL-1 by atmospheric and room temperature plasma mutagenesis and streptomycin resistance screening. Ann Microbiol, 2015, 65: 2009-2017.

[72] Wang J, Zhang Z, Liu H, Sun FF, Yue C, Hu J, Wang C. Construction and optimization of trans-4-hydroxy-l-proline production recombinant E. coli strain taking the glycerol as carbon source. J Chem Technol Biotechnol, 2016, 91: 2389-2398.

[73] Wang L, Chen X, Wu G, Zeng X, Ren X, Li S, Tang L, Mao Z. Genome shuffling and gentamicin-resistance to improve ε-poly-l-lysine productivity of Streptomyces albulus W-156. Appl Biochem Biotechnol, 2016, 180: 1601-1617.

[74] Wang Y, Li Q, Zheng P, Guo Y, Wang L, Zhang T, Sun J, Ma T. Evolving the l-lysine high-producing strain of Escherichia coli using a newly developed high-throughput screening method. J Ind Microbiol Biotechnol, 2016, 43: 1227-1235.

[75] Wang Q, Liu D, Yang Q, Wang P. Enhancing carotenoid production in Rhodotorula mucilaginosa KC8 by combining mutation and metabolic engineering. Ann Microbiol, 2017, 67: 425-431.

[76] Winter T, Bernhardt J, Winter J, Mäder U, Schlüter R, Weltmann KD, Hecker M, Kusch H. Common versus noble Bacillus subtilis differentially responds to air and argon gas plasma. Proteomics, 2013, 13: 2608-2621.

[77] Wu X, Wei Y, Xu Z, Liu L, Tan Z, Jia S. Evaluation of an ethanol-tolerant Acetobacter pasteurianus mutant generated by a new atmospheric and room temperature plasma (ARTP). Lect Notes Electr Eng, 2015, 333: 277-286.

[78] Xu J, Zhang W. Menaquinone-7 production from maize meal hydrolysate by Bacillus isolates with diphenylamine and analogue resistance. J Zhejiang Univ Sci B, 2017, 18: 462-473.

[79] Xu F, Wang J, Chen S, Qin W, Yu Z, Zhao H, Xing X, Li H. Strain improvement for enhanced production of cellulase in Trichoderma viride. Appl Biochem Microbiol, 2011, 47: 53-58.

[80] Xu F, Jin H, Li H, Tao L, Wang J, Lv J, Chen S. Genome shuffling of Trichoderma viride for enhanced cellulase production. Ann Microbiol, 2012, 62: 509-515.

[81] Xu J, Han M, Ren X, Zhang W. Modification of aspartokinase III and dihydrodipicolinate synthetase increases the production of l-lysine in Escherichia coli. Biochem Eng J, 2016, 114: 79-86.

[82] Xu C, He S, Liu Y, Zhang W, Lu D. Bioadsorption and biostabilization of cadmium by Enterobacter cloacae TU. Chemosphere, 2017, 173: 622-629.

[83] Xu J, Zhou S, Zhao Y, Xia J, Liu X, Xu JM, He B, Wu B, Zhang J. Asymmetric whole-cell bioreduction of sterically bulky 2-benzoylpyridine derivatives in aqueous hydrophilic ionic liquid media. Chem Eng J, 2017, 316: 919-927.

[84] Xu W, Jia H, Zhang L, Wang H, Tang H, Zhang L. Effects of GSH1 and GSH2 gene mutation on glutathione synthetases activity of Saccharomyces cerevisiae. Protein J, 2017, 36: 270-277.

[85] Yolmeh M, Khomeiri M. Effect of mutagenesis treatment on antimicrobial and antioxidant activities of pigments extracted from Rhodotorula glutinis. Biocatal Agric Biotechnol, 2017, 10: 285-290.

[86] Zeng W, Du G, Chen J, Li J, Zhou J. A high-throughput screening procedure for enhancing alpha-ketoglutaric acid production in Yarrowia lipolytica by random mutagenesis. Process Biochem, 2015, 50: 1516-1522.

[87] Zeng W, Fang F, Liu S, Du G, Chen J, Zhou J. Comparative genomics analysis of a series of Yarrowia lipolytica WSH-Z06 mutants with varied capacity for α-ketoglutarate production. J Biotechnol, 2016, 239: 76-82.

[88] Zhang X, Zhang XF, Li HP, Wang LY, Zhang C, Xing XH, Bao CY. Atmospheric and room temperature plasma (ARTP) as a new powerful mutagenesis tool. Appl Microbiol Biotechnol, 2014, 98: 5387-5396.

[89] Zhang D, Wang Q, Liang X. Breeding high producers of enduracidin from Streptomyces fungicidicus by combination of various mutation treatments. Lect Notes Electr Eng, 2015, 332: 133-142.

[90] Zhang G, Lin Y, Qi X, Wang L, He P, Wang Q, Ma Y. Genome shuffling of the nonconventional yeast Pichia anomala for improved sugar alcohol production. Microb Cell Fact, 2015, 14: 112.

[91] Zhang X, Zhang C, Zhou QQ, Zhang XF, Wang LY, Chang HB, Li HP, Oda Y, Xing XH. Quantitative evaluation of DNA damage and mutation rate by atmospheric and room-temperature plasma (ARTP) and conventional mutagenesis. Appl Microbiol Biotechnol, 2015, 99: 5639-5646.

[92] Zhang C, Shen H, Zhang X, Yu X, Wang H, Xiao S, Wang J, Zhao ZK. Combined mutagenesis of Rhodosporidium toruloides for improved production of carotenoids and lipids. Biotechnol Lett, 2016, 38: 1733-1738.

[93] Zheng Z, Cai C, Jiang T, Zhao M, Ouyang J. Enhanced l-lactic acid production from biomass-derived xylose by a mutant Bacillus coagulans. Appl Biochem Biotechnol, 2014, 173: 1896-1906.

[94] Zhu L, Xu Q, Jiang L, Huang H, Li S. Polydiacetylene-based high-throughput screen for surfactin producing strains of Bacillus subtilis. PLoS ONE, 2014, 9: e88207.

[95] Zhu P, Chen X, Li S, Xu H, Dong S, Xu Z, Zhang Y. Screening and characterization of Sphingomonas sp. mutant for welan gum biosynthesis at an elevated temperature. Bioprocess Biosyst Eng, 2014, 37: 1849-1858.

[96] Zhu X, Arman B, Chu J, Wang Y, Zhuang Y. Development of a method for efficient cost-effective screening of Aspergillus niger mutants having increased production of glucoamylase. Biotechnol Lett, 2017, 39: 739-744.

[97] Zong H, Zhan Y, Li X, Peng L, Feng F, Li D. A new mutation breeding method for Streptomyces albulus by an atmospheric and room temperature plasma. Afr J Microbiol Res, 2012, 6: 3154-3158.