Progress and perspective on lignocellulosic hydrolysate inhibitor tolerance improvement in Zymomonas mobilis

Abstract

Pretreatment is the key step to overcome the recalcitrance of lignocellulosic biomass making sugars available for subsequent enzymatic hydrolysis and microbial fermentation. During the process of pretreatment and enzymatic hydrolysis as well as fermentation, various toxic compounds may be generated with strong inhibition on cell growth and the metabolic capacity of fermenting strains. Zymomonas mobilis is a natural ethanologenic bacterium with many desirable industrial characteristics, but it can also be severely affected by lignocellulosic hydrolysate inhibitors. In this review, analytical methods to identify and quantify potential inhibitory compounds generated during lignocellulose pretreatment and enzymatic hydrolysis were discussed. The effect of hydrolysate inhibitors on Z. mobilis was also summarized as well as corresponding approaches especially the high-throughput ones for the evaluation. Then the strategies to enhance inhibitor tolerance of Z. mobilis were presented, which include both forward and reverse genetics approaches such as classical and novel mutagenesis approaches, adaptive laboratory evolution, as well as genetic and metabolic engineering. Moreover, this review provided perspectives and guidelines for future developments of robust strains for efficient bioethanol or biochemical production from lignocellulosic materials.

Keywords

Lignocellulose / Inhibitor / Zymomonas mobilis / Robustness / Adaptive laboratory evolution (ALE) / Mutagenesis / Systems biology / Metabolic engineering

References

[1] Almeida JRM, Modig T, Petersson A, Hahn-Hagerdal B, Liden G, Gorwa-Grauslund MF. Increased tolerance and conversion of inhibitors in lignocellulosic hydrolysates by Saccharomyces cerevisiae. J Chem Technol Biotechnol, 2007, 82: 340-349.

[2] Alper H, Stephanopoulos G. Global transcription machinery engineering: a new approach for improving cellular phenotype. Metab Eng, 2007, 9: 258-267.

[3] Baral NR, Li JZ, Jha AK. Perspective and prospective of pretreatment of corn straw for butanol production. Appl Biochem Biotechnol, 2014, 172: 840-853.

[4] Bochner B, Gomez V, Ziman M, Yang S, Brown SD. Phenotype microarray profiling of Zymomonas mobilis ZM4. Appl Biochem Biotechnol, 2010, 161: 116-123.

[5] Bothast RJ, Nichols NN, Dien BS. Fermentations with new recombinant organisms. Biotechnol Prog, 1999, 15: 867-875.

[6] Buchholz S, Eveleigh D. Genetic modification of Zymomonas mobilis. Biotechnol Adv, 1990, 8: 547-581.

[7] Cao QH, Shao HH, Qiu H, Li T, Zhang YZ, Tan XM. Using the CRISPR/Cas9 system to eliminate native plasmids of Zymomonas mobilis ZM4. Biosci Biotechnol Biochem, 2017, 81: 453-459.

[8] 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.

[9] Capolupo L, Faraco V. Green methods of lignocellulose pretreatment for biorefinery development. Appl Microbiol Biotechnol, 2016, 100: 9451-9467.

[10] Chen XG. Economic potential of biomass supply from crop residues in China. Appl Energy, 2016, 166: 141-149.

[11] Chen X, Tao L, Joseph S, Ali M, Steve D, Wang W, Holly S, Sunkyu P, Himmel ME, Melvin T. Improved ethanol yield and reduced Minimum Ethanol Selling Price (MESP) by modifying low severity dilute acid pretreatment with deacetylation and mechanical refining: 1) Experimental. Biotechnol Biofuels, 2012, 5: 69.

[12] Chen X, Kuhn E, Jennings E, Nelson R, Zhang M, Ciesielski PN, Tao L, Tucker MP. DMR (deacetylation and mechanical refining) processing of corn stover achieves high monomeric sugar concentrations (230 g/L) during enzymatic hydrolysis and high ethanol concentration (> 10% v/v) during fermentation without hydrolyzate purification or conce. Energ Environ Sci, 2016, 9: 1237-1245.

[13] Cho SH, Lei R, Henninger TD, Contreras LM. Discovery of ethanol-responsive small RNAs in Zymomonas mobilis. Appl Environ Microbiol, 2014, 80: 4189-4198.

[14] Cho SH, Haning K, Shen W, Blome C, Yang S, Contreras L. Identification and characterization of 5′untranslated regions (5′UTRs) in Zymomonas mobilis as regulatory biological parts. Front Microbiol, 2017, 8: 2432.

[15] Deanda K, Zhang M, Eddy C, Picataggio S. Development of an arabinose-fermenting Zymomonas mobilis strain by metabolic pathway engineering. Appl Environ Microbiol, 1996, 62: 4465-4470.

[16] Delgenes JP, Moletta R, Navarro JM. Effects of lignocellulose degradation products on ethanol fermentations of glucose and xylose by Saccharomyces cerevisiae, Zymomonas mobilis, Pichia stipitis, and Candida shehatae. Enzyme Microb Technol, 1996, 19: 220-225.

[17] Dong HW, Fan LQ, Luo Z, Zhong JJ, Ryu DD, Bao J. Improvement of ethanol productivity and energy efficiency by degradation of inhibitors using recombinant Zymomonas mobilis (pHW20a-fdh). Biotechnol Bioeng, 2013, 110: 2395-2404.

[18] Dong G, He M, Feng H. Functional characterization of CRISPR-Cas system in the ethanologenic bacterium Zymomonas mobilis ZM4. Adv Microbiol, 2016, 06: 178-189.

[19] Dragosits M, Mattanovich D. Adaptive laboratory evolution—principles and applications for biotechnology. Microbl Cell Fact, 2013, 12: 64.

[20] Dunn KL, Rao CV. Expression of a xylose-specific transporter improves ethanol production by metabolically engineered Zymomonas mobilis. Appl Microbiol Biotechnol, 2014, 98: 6897-6905.

[21] Feng Q, Li S, Wang L, Li T. Evaluation on glucose–xylose co-fermentation by a recombinant Zymomonas mobilis strain. Sheng Wu Gong Cheng Xue Bao, 2012, 28: 37-47.

[22] Franden MA, Pienkos PT, Zhang M. Development of a high-throughput method to evaluate the impact of inhibitory compounds from lignocellulosic hydrolysates on the growth of Zymomonas mobilis. J Biotechnol, 2009, 144: 259-267.

[23] Franden MA, Pilath HM, Mohagheghi A, Pienkos PT, Zhang M. Inhibition of growth of Zymomonas mobilis by model compounds found in lignocellulosic hydrolysates. Biotechnol Biofuels, 2013, 6: 99.

[24] Gan M, Su J, Wang J, Wu H, Chen L. A scalable microfluidic chip for bacterial suspension culture. Lab Chip, 2011, 11: 4087-4092.

[25] Gu H, Zhang J, Bao J. Inhibitor analysis and adaptive evolution of Saccharomyces cerevisiae for simultaneous saccharification and ethanol fermentation from industrial waste corncob residues. Bioresour Technol, 2014, 157: 6-13.

[26] Gu H, Zhang J, Bao J. High tolerance and physiological mechanism of Zymomonas mobilis to phenolic inhibitors in ethanol fermentation of corncob residue. Biotechnol Bioeng, 2015, 112: 1770-1782.

[27] Hayashi T, Kato T, Watakabe S, Song W, Aikawa S, Furukawa K. The respiratory chain provides salt stress tolerance by maintaining a low NADH/NAD⁺ ratio in Zymomonas mobilis. Microbiology, 2015, 161: 2384-2394.

[28] He MX, Wu B, Shui ZX, Hu QC, Wang WG, Tan FR, Tang XY, Zhu QL, Pan K, Li Q, Su XH. Transcriptome profiling of Zymomonas mobilis under furfural stress. Appl Microbiol Biotechnol, 2012, 95: 189-199.

[29] He MX, Wu B, Qin H, Ruan ZY, Tan FR, Wang JL, Shui ZX, Dai LC, Zhu QL, Pan K, Tang XY, Wang WG, Hu QC. Zymomonas mobilis: a novel platform for future biorefineries. Biotechnol Biofuels, 2014, 7: 101.

[30] Jennings EW, Schell DJ. Conditioning of dilute-acid pretreated corn stover hydrolysate liquors by treatment with lime or ammonium hydroxide to improve conversion of sugars to ethanol. Bioresour Technol, 2011, 102: 1240-1245.

[31] Jeon YJ, Xun Z, Rogers PL. Comparative evaluations of cellulosic raw materials for second generation bioethanol production. Lett Appl Microbiol, 2010, 51: 518-524.

[32] Jia X, Wei N, Wang T, Wang H. Use of an EZ-Tn5-based random mutagenesis system to create a Zymomonas mobilis with significant tolerance to heat stress and malnutrition. J Ind Microbiol Biotechnol, 2013, 40: 811-822.

[33] 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.

[34] Jin M, Bothfeld W, Austin S, Sato TK, La Reau A, Li H, Foston M, Gunawan C, LeDuc RD, Quensen JF, McGee M, Uppugundla N, Higbee A, Ranatunga R, Donald CW, Bone G, Ragauskas AJ, Tiedje JM, Noguera DR, Dale BE, Zhang Y, Balan V. Effect of storage conditions on the stability and fermentability of enzymatic lignocellulosic hydrolysate. Bioresour Technol, 2013, 147: 212-220.

[35] Joachimsthal E, Haggett KD, Jang JH, Rogers PL. A mutant of Zymomonas mobilis ZM4 capable of ethanol production from glucose in the presence of high acetate concentrations. Biotechnol Lett, 1998, 20: 137-142.

[36] Joachimsthal E, Haggett KD, Rogers PL. Evaluation of recombinant strains of Zymomonas mobilis for ethanol production from glucose/xylose media. Appl Biochem Biotechnol, 1999, 99: 77-79.

[37] Jönsson LJ, Alriksson B, Nilvebrant NO. Bioconversion of lignocellulose: inhibitors and detoxification. Biotechnol Biofuels, 2013, 6: 16.

[38] Kalnenieks U, Pentjuss A, Rutkis R, Stalidzans E, Fell DA. Modeling of Zymomonas mobilis central metabolism for novel metabolic engineering strategies. Front Microbiol, 2014, 5: 42.

[39] Kim IS, Barrow KD, Rogers PL. Nuclear magnetic resonance studies of acetic acid inhibition of rec Zymomonas mobilis ZM4(pZB5). Appl Biochem Biotechnol, 2000, 84–86: 357-370.

[40] Klinke HB, Thomsen AB, Ahring BK. Inhibition of ethanol-producing yeast and bacteria by degradation products produced during pre-treatment of biomass. Appl Microbiol Biotechnol, 2004, 66: 10-26.

[41] Krishnan MS, Blanco M, Shattuck CK, Nghiem NP, Davison BH. Ethanol production from glucose and xylose by immobilized Zymomonas mobilis CP4 (pZB5). Appl Biochem Biotechnol, 2000, 84-86(1-9): 525-541.

[42] Le DM, Sorensen HR, Knudsen NO, Schjoerring JK, Meyer AS. Biorefining of wheat straw: accounting for the distribution of mineral elements in pretreated biomass by an extended pretreatment-severity equation. Biotechnol Biofuels, 2014, 7: 141.

[43] Lee JH, Skotnicki ML, Rogers PL. Kinetic studies on a flocculent strain of Zymomonas mobilis. Biotechnol Lett, 1982, 4: 615-620.

[44] Lee H, Popodi E, Tang H, Foster PL. Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing. Proc Natl Acad Sci USA, 2012, 109: E2774-E2783.

[45] Li XZ, Webb JS, Kjelleberg S, Rosche B. Enhanced benzaldehyde tolerance in Zymomonas mobilis biofilms and the potential of biofilm applications in fine-chemical production. Appl Environ Microbiol, 2006, 72: 1639-1644.

[46] Liu YF, Hsieh CW, Chang YS, Wung BS. Effect of acetic acid on ethanol production by Zymomonas mobilis mutant strains through continuous adaptation. BMC Biotechnol, 2017, 17: 63.

[47] Madren SM, Hoffman MD, Brown PJ, Kysela DT, Brun YV, Jacobson SC. Microfluidic device for automated synchronization of bacterial cells. Anal Chem, 2012, 84: 8571-8578.

[48] Mohagheghi A, Evans K, Chou YC, Zhang M. Cofermentation of glucose, xylose, and arabinose by genomic DNA-integrated xylose/arabinose fermenting strain of Zymomonas mobilis AX101. Appl Biochem Biotechnol, 2002, 98–100: 885-898.

[49] Mohagheghi A, Dowe N, Schell D, Chou YC, Eddy C, Zhang M. Performance of a newly developed integrant of Zymomonas mobilis for ethanol production on corn stover hydrolysate. Biotechnol Lett, 2004, 26: 321-325.

[50] Mohagheghi A, Linger J, Smith H, Yang S, Dowe N, Pienkos PT. Improving xylose utilization by recombinant Zymomonas mobilis strain 8b through adaptation using 2-deoxyglucose. Biotechnol Biofuels, 2014, 7: 19.

[51] Mohagheghi A, Linger JG, Yang SH, Smith H, Dowe N, Zhang M, Pienkos PT. Improving a recombinant Zymomonas mobilis strain 8b through continuous adaptation on dilute acid pretreated corn stover hydrolysate. Biotechnol Biofuels, 2015, 8: 55.

[52] Olsson L, Hahn-Hägerdal B. Fermentation of lignocellulosic hydrolysates for ethanol production. Enzyme Microb Technol, 1996, 18: 312-331.

[53] Panesar PS, Marwaha SS, Kennedy JF. Zymomonas mobilis: an alternative ethanol producer. J Chem Technol Biotechnol, 2006, 81: 623-635.

[54] Pappas K, Galani I, Typas M. Transposon mutagenesis and strain construction in Zymomonas mobilis. J Appl Microbiol, 1997, 82: 379-388.

[55] Parawira W, Tekere M. Biotechnological strategies to overcome inhibitors in lignocellulose hydrolysates for ethanol production: review. Crit Rev Biotechnol, 2011, 31: 20-31.

[56] Pentjuss A, Odzina I, Kostromins A, Fell DA, Stalidzans E, Kalnenieks U. Biotechnological potential of respiring Zymomonas mobilis: a stoichiometric analysis of its central metabolism. J Biotechnol, 2013, 165: 1-10.

[57] Portnoy VA, Bezdan D, Zengler K. Adaptive laboratory evolution-harnessing the power of biology for metabolic engineering. Curr Opin Biotechnol, 2011, 22: 590-594.

[58] Rogers PL, Skotnicki ML, Lee KJ, Lee JH. Recent developments in the Zymomonas process for ethanol production. Crit Rev Biotechnol, 1984, 1: 273-288.

[59] Rogers PL, Jeon YJ, Lee KJ, Lawford HG. Zymomonas mobilis for fuel ethanol and higher value products. Adv Biochem Eng Biotechnol, 2007, 108: 263-288.

[60] Schell DJ, Dowe N, Chapeaux A, Nelson RS, Jennings EW. Accounting for all sugars produced during integrated production of ethanol from lignocellulosic biomass. Bioresour Technol, 2016, 205: 153-158.

[61] Seo JS, Chong H, Park HS, Yoon KO, Jung C, Kim JJ, Hong JH, Kim H, Kim JH, Kil JI, Park CJ, Oh HM, Lee JS, Jin SJ, Um HW, Lee HJ, Oh SJ, Kim JY, Kang HL, Lee SY, Lee KJ, Kang HS. The genome sequence of the ethanologenic bacterium Zymomonas mobilis ZM4. Nat Biotechnol, 2005, 23: 63-68.

[62] Serate J, Xie D, Pohlmann E, Donald C Jr, Shabani M, Hinchman L, Higbee A, McGee M, La Reau A, Klinger GE, Li S, Myers CL, Boone C, Bates DM, Cavalier D, Eilert D, Oates LG, Sanford G, Sato TK, Dale B, Landick R, Piotrowski J, Ong RG, Zhang Y. Controlling microbial contamination during hydrolysis of AFEX-pretreated corn stover and switchgrass: effects on hydrolysate composition, microbial response and fermentation. Biotechnol Biofuels, 2015, 8: 180.

[63] Shi J, Pu Y, Yang B, Ragauskas A, Wyman CE. Comparison of microwaves to fluidized sand baths for heating tubular reactors for hydrothermal and dilute acid batch pretreatment of corn stover. Bioresour Technol, 2011, 102: 5952-5961.

[64] Shui ZX, Qin H, Wu B, Ruan ZY, Wang LS, Tan FR, Wang JL, Tang XY, Dai LC, Hu GQ, He MX. Adaptive laboratory evolution of ethanologenic Zymomonas mobilis strain tolerant to furfural and acetic acid inhibitors. Appl Microbiol Biotechnol, 2015, 99: 5739-5748.

[65] Silveira MHL, Morais ARC, Lopes AMD, Olekszyszen DN, Bogel-Lukasik R, Andreaus J, Ramos LP. Current pretreatment technologies for the development of cellulosic ethanol and biorefineries. Chemsuschem, 2015, 8: 3366-3390.

[66] Skerker JM, Leon D, Price MN, Mar JS, Tarjan DR, Wetmore KM, Deutschbauer AM, Baumohl JK, Bauer S, Ibanez AB, Mitchell VD, Wu CH, Hu P, Hazen T, Arkin AP. Dissecting a complex chemical stress: chemogenomic profiling of plant hydrolysates. Mol Syst Biol, 2013, 9: 674.

[67] Sun Y, Cheng J. Hydrolysis of lignocellulosic materials for ethanol production: a review. Bioresour Technol, 2002, 83: 1-11.

[68] Sun S, Cao X, Sun R. The role of pretreatment in improving the enzymatic hydrolysis of lignocellulosic materials. Bioresour Technol, 2016, 199: 49-58.

[69] Tan FR, Dai LC, Wu B, Qin H, Shui ZX, Wang JL, Zhu QL, Hu QC, Ruan ZY, He MX. Improving furfural tolerance of Zymomonas mobilis by rewiring a sigma factor RpoD protein. Appl Microbiol Biotechnol, 2015, 99: 5363-5371.

[70] Tan F, Wu B, Dai L, Qin H, Shui Z, Wang J, Zhu Q, Hu G, He M. Using global transcription machinery engineering (gTME) to improve ethanol tolerance of Zymomonas mobilis. Microb Cell Fact, 2016, 15: 4.

[71] Teixeira LC, Linden JC, Schroeder HA. Simultaneous saccharification and cofermentation of peracetic acid-pretreated biomass. Appl Biochem Biotechnol, 2000, 84–86: 111-127.

[72] Todhanakasem T, Sangsutthiseree A, Areerat K, Young GM, Thanonkeo P. Biofilm production by Zymomonas mobilis enhances ethanol production and tolerance to toxic inhibitors from rice bran hydrolysate. New Biotechnol, 2014, 31: 451-459.

[73] Todhanakasem T, Narkmit T, Areerat K, Thanonkeo P. Fermentation of rice bran hydrolysate to ethanol using Zymomonas mobilis biofilm immobilization on DEAE-cellulose. Electron J Biotechnol, 2015, 18: 196-201.

[74] Todhanakasem T, Yodsanga S, Sowatad A, Kanokratana P, Thanonkeo P, Champreda V. Inhibition analysis of inhibitors derived from lignocellulose pretreatment on the metabolic activity of Zymomonas mobilis biofilm and planktonic cells and the proteomic responses. Biotechnol Bioeng, 2018, 115: 70-81.

[75] Typas MA, Galani I. Chemical and UV mutagenesis in Zymomonas mobilis. Genetica, 1992, 87: 37-45.

[76] Viitanen PV, Tao L, Knoke K, Zhang Y, Caimi PG, Zhang M, Chou YC, Franden MA (2009) Process for the production of ethanol from a medium comprising xylose, employing a recombinant Zymomonas strain having a reduced himA expression. WO Patent 2009058938 A2 2009

[77] Viitanen PV, Tao L, Knoke K, Zhang Y, Caimi PG, Zhang M, Chou YC, Franden MA (2012) Zymomonas with improved ethanol production in medium containing concentrated sugars and acetate. EP Patent 2209899 B1 2012

[78] Wang Y. Development of acetic-acid tolerant Zymomonas mobilis strains through adaptation, 2008, Atlanta: Georgia Institute of Technology.

[79] Wang W, Yang S, Hunsinger GB, Pienkos PT, Johnson DK. Connecting lignin-degradation pathway with pre-treatment inhibitor sensitivity of Cupriavidus necator. Front Microbiol, 2014, 5: 247.

[80] Wang JL, Wu B, Qin H, You Y, Liu S, Shui ZX, Tan FR, Wang YW, Zhu QL, Li YB, Ruan ZY, Ma KD, Dai LC, Hu GQ, He MX. Engineered Zymomonas mobilis for salt tolerance using EZ-Tn5-based transposon insertion mutagenesis system. Microbl Cell Fact, 2016, 15: 101.

[81] Wang X, Gao Q, Bao J. Enhancement of furan aldehydes conversion in Zymomonas mobilis by elevating dehydrogenase activity and cofactor regeneration. Biotechnol Biofuels, 2017, 10: 24.

[82] Widiastuti H, Kim JY, Selvarasu S, Karimi IA, Kim H, Seo JS, Lee DY. Genome-scale modeling and in silico analysis of ethanologenic bacteria Zymomonas mobilis. Biotechnol Bioeng, 2011, 108: 655-665.

[83] Wu Y, Li BZ, Zhao M, Mitchell LA, Xie ZX, Lin QH, Wang X, Xiao WH, Wang Y, Zhou X, Liu H, Li X, Ding MZ, Liu D, Zhang L, Liu BL, Wu XL, Li FF, Dong XT, Jia B, Zhang WZ, Jiang GZ, Liu Y, Bai X, Song TQ, Chen Y, Zhou SJ, Zhu RY, Gao F, Kuang Z, Wang X, Shen M, Yang K, Stracquadanio G, Richardson SM, Lin Y, Wang L, Walker R, Luo Y, Ma PS, Yang H, Cai Y, Dai J, Bader JS, Boeke JD, Yuan YJ. Bug mapping and fitness testing of chemically synthesized chromosome X. Science, 2017, 355: eaaf4706.

[84] Xie ZX, Li BZ, Mitchell LA, Wu Y, Qi X, Jin Z, Jia B, Wang X, Zeng BX, Liu HM, Wu XL, Feng Q, Zhang WZ, Liu W, Ding MZ, Li X, Zhao GR, Qiao JJ, Cheng JS, Zhao M, Kuang Z, Martin JA, Stracquadanio G, Yang K, Bai X, Zhao J, Hu ML, Lin QH, Zhang WQ, Shen MH, Chen S, Su W, Wang EX, Guo R, Zhai F, Guo XJ, Du HX, Zhu JQ, Song TQ, Dai JJ, Li FF, Jiang GZ, Han SL, Liu SY, Yu ZC, Yang XN, Chen K, Hu C, Li DS, Jia N, Liu Y, Wang LT, Wang S, Wei XT, Fu MQ, Qu LM, Xin SY, Liu T, Tian KR, Li XN, Zhang JH, Song LX, Liu JG, Lv JF, Xu H, Tao R, Wang Y, Zhang TT, Deng YX, Wang YR, Li T, Ye GX, Xu XR, Xia ZB, Zhang W, Yang SL, Liu YL, Ding WQ, Liu ZN, Liu NZ, Walker R, Luo Y, Shen Y, Yang H, Cai Y, Ma PS, Zhang CT, Bader JS, Boeke JD, Yuan YJ. “Perfect” designer chromosome V and behavior of a ring derivative. Science., 2017, 355: eaaf4704.

[85] Yadav VG, De Mey M, Lim CG, Ajikumar PK, Stephanopoulos G. The future of metabolic engineering and synthetic biology: towards a systematic practice. Metab Eng, 2012, 14: 233-241.

[86] Yanase H, Miyawaki H, Sakurai M, Kawakami A, Matsumoto M, Haga K, Kojima M, Okamoto K. Ethanol production from wood hydrolysate using genetically engineered Zymomonas mobilis. Appl Microbiol Biotechnol, 2012, 94: 1667-1678.

[87] Yang S, Pappas KM, Hauser LJ, Land ML, Chen GL, Hurst GB, Pan C, Kouvelis VN, Typas MA, Pelletier DA, Klingeman DM, Chang YJ, Samatova NF, Brown SD. Improved genome annotation for Zymomonas mobilis. Nat Biotechnol, 2009, 27: 893-894.

[88] Yang S, Tschaplinski TJ, Engle NL, Carroll SL, Martin SL, Davison BH, Palumbo AV, Rodriguez M Jr, Brown SD. Transcriptomic and metabolomic profiling of Zymomonas mobilis during aerobic and anaerobic fermentations. BMC Genom, 2009, 10: 34.

[89] Yang S, Land ML, Klingeman DM, Pelletier DA, Lu TY, Martin SL, Guo HB, Smith JC, Brown SD. Paradigm for industrial strain improvement identifies sodium acetate tolerance loci in Zymomonas mobilis and Saccharomyces cerevisiae. Proc Natl Acad Sci USA, 2010, 107: 10395-10400.

[90] Yang S, Pelletier DA, Lu T-YS, Brown SD. The Zymomonas mobilis regulator hfq contributes to tolerance against multiple lignocellulosic pretreatment inhibitors. BMC Microbiol, 2010, 10: 135.

[91] Yang S, Franden MA, Brown SD, Chou YC, Pienkos PT, Zhang M. Insights into acetate toxicity in Zymomonas mobilis 8b using different substrates. Biotechnol Biofuels, 2014, 7: 140.

[92] Yang S, Linger J, Franden MA, Pienkos PT, Zhang M (2014b) Biocatalysts with enhanced inhibitor tolerance, vol US9206445

[93] Yang S, Pan C, Hurst GB, Dice L, Davison BH, Brown SD. Elucidation of Zymomonas mobilis physiology and stress responses by quantitative proteomics and transcriptomics. Front Microbiol, 2014, 5: 246.

[94] Yang S, Fei Q, Zhang Y, Contreras LM, Utturkar SM, Brown SD, Himmel ME, Zhang M. Zymomonas mobilis as a model system for production of biofuels and biochemicals. Microb Biotechnol, 2016, 9: 699-717.

[95] Yi X, Gu H, Gao Q, Liu ZL, Bao J. Transcriptome analysis of Zymomonas mobilis ZM4 reveals mechanisms of tolerance and detoxification of phenolic aldehyde inhibitors from lignocellulose pretreatment. Biotechnol Biofuels, 2015, 8: 153.

[96] Zaldivar J, Martinez A, Ingram LO. Effect of selected aldehydes on the growth and fermentation of ethanologenic Escherichia coli. Biotechnol Bioeng, 1999, 65: 24-33.

[97] Zhang M, Eddy C. Metabolic engineering of a pentose metabolism pathway in ethanologenic Zymomonas mobilis. Science, 1995, 267: 240-243.

[98] Zhang Y, Ma RQ, Zhao ZL, Zhou ZF, Lu W, Zhang W, Chen M. irrE, an exogenous gene from Deinococcus radiodurans, improves the growth of and ethanol production by a Zymomonas mobilis strain under ethanol and acid stresses. J Microbiol Biotechnol, 2010, 20: 1156-1162.

[99] Zhang X, Zhang X-F, 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.

[100] 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.

[101] Zhang WM, Zhao GH, Luo ZQ, Lin YC, Wang LH, Guo YK, Wang A, Jiang SY, Jiang QW, Gong JH, Wang Y, Hou S, Huang J, Li TY, Qin YR, Dong JK, Qin Q, Zhang JY, Zou XZ, He X, Zhao L, Xiao YB, Xu M, Cheng EC, Huang N, Zhou T, Shen Y, Walker R, Luo YS, Kuang Z, Mitchell LA, Yang K, Richardson SM, Wu Y, Li BZ, Yuan YJ, Yang HM, Lin JW, Chen GQ, Wu QY, Bader JS, Cai YZ, Boeke JD, Dai JB. Engineering the ribosomal DNA in a megabase synthetic chromosome. Science, 2017, 355: eaaf3981.

[102] Zhao N, Bai Y, Zhao XQ, Yang ZY, Bai FW. Draft genome sequence of the flocculating Zymomonas mobilis strain ZM401 (ATCC 31822). J Bacteriol, 2012, 194: 7008-7009.

[103] Zhao N, Bai Y, Liu CG, Zhao XQ, Xu JF, Bai FW. Flocculating Zymomonas mobilis is a promising host to be engineered for fuel ethanol production from lignocellulosic biomass. Biotechnol J, 2014, 9: 362-371.