Review Open Access

Tolerance in Solventogenic Clostridia for Enhanced Butanol Production: Genetic Mechanisms and Recent Strain Engineering Advances

Synthetic Biology and Engineering. 2024, 2(2), 10007; https://doi.org/10.35534/sbe.2024.10007
1
Department of Biosystems Engineering, Auburn University, Auburn, AL 36849, USA
2
Universidad Nacional (UNA), Omar Dengo Campus, Heredia, 40101, Costa Rica
3
Environmental Microbiology Group, Northwestern Center for Biological Research (CIBNOR), Av. IPN 195, La Paz, B.C.S. 23096, Mexico
4
The Bashan Institute of Science, 1730 Post Oak Court, Auburn AL 36830, USA
5
Department of Entomology and Plant Pathology, Auburn University, Auburn, AL 36849, USA
6
The key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China
7
Center for Bioenergy and Bioproducts, Auburn University, Auburn, AL 36849, USA
8
Current address: Department of Biological and Agricultural Engineering, University of California, Davis, 1 Shields Ave, Davis, CA, 95616 USA
*
Authors to whom correspondence should be addressed.

Received: 02 Feb 2024    Accepted: 01 Apr 2024    Published: 08 Apr 2024   

Abstract

Biobutanol is a promising candidate for replacing fossil fuels due to its superior properties compared to ethanol. Solventogenic clostridia can naturally produce biobutanol among other valuable chemicals. Lignocellulosic material stands out as a promising source for biobutanol production, avoiding competition with food production and making use of residues from both agroindustry and forestry activities. However, Clostridium strains are subject to different chemical stressors, including oxygen, self-product inhibition, inhibitors generated during biomass pretreatment and hydrolysis, and others. Recent advances in genetic engineering tools have enabled the metabolic engineering of Clostridium strains to increase their robustness and tolerance to these stressors. This review provides a summary of the various types of inhibitors, the genetic mechanisms related to tolerance, and recent strain engineering efforts for tolerance enhancement. In addition, we offer a valuable perspective on the future research directions in this area.

References

1.
Patakova, P, Kolek, J, Sedlar, K, Koscova, P, Branska, B, Kupkova, K, et al. Comparative analysis of high butanol tolerance and production in clostridia.  Biotech. Adv. 2018, 36, 721–738. [Google Scholar]
2.
Liu, S, Qureshi, N, Hughes, S.R. Progress and perspectives on improving butanol tolerance.  World J. Microb. Biotech. 2017, 33, 51. [Google Scholar]
3.
Wang S, Sun X, Yuan Q. Strategies for enhancing microbial tolerance to inhibitors for biofuel production: A review.  Bioresour. Tech. 2018, 258, 302–309. [Google Scholar]
4.
Amiri H, Karimi K. Pretreatment and Hydrolysis of Lignocellulosic Wastes for Butanol Production: Challenges and Perspectives.  Bioresour. Tech. 2018, 270, 702–721. [Google Scholar]
5.
Kim D. Physico-chemical conversion of lignocellulose: Inhibitor effects and detoxification strategies: A mini review.  Molecules 2018, 23, 309. [Google Scholar]
6.
Maddox I, Steiner E, Hirsch S, Wessner S, Gutierrez N, Gapes J, et al. The Cause of "Acid Crash" and "Acidogenic Fermentations" During the Batch Acetone-Butanol-Ethanol(ABE-) Fermentation Process.  J. Mol. Microbiol. Biotech. 2000, 2, 95–100. [Google Scholar]
7.
Reed W, Keller F, Kite F, Bogdan M, Ganoung J. Development of increased acetic acid tolerance in anaerobic homoacetogens through induced mutagenesis and continuous selection.  Enzyme Microb. Tech. 1987, 9, 117–120. [Google Scholar]
8.
Wang P. Engineering Clostridium saccharoperbutylacetonicum for enhanced isopropanol-butanolethanol (IBE) production from lignocellulosic biomass through acetic acid pretreatment. Dissertation for Doctoral Degree; Auburn University: Auburn, AL USA; 2018.
9.
Bengelsdorf FR, Poehlein A, Linder S, Erz C, Hummel T, Hoffmeister S, et al. Industrial acetogenic biocatalysts: a comparative metabolic and genomic analysis.  Front. Microbiol. 2016, 7, 1036. [Google Scholar]
10.
Schwartz RD, Keller FA. Acetic acid production by Clostridium thermoaceticum in pH-controlled batch fermentations at acidic pH.  Appl. Environ. Microbiol. 1982, 43, 1385–1392. [Google Scholar]
11.
Gößner AS, Picardal F, Tanner RS, Drake HL.  Carbon metabolism of the moderately acid-tolerant acetogen Clostridium drakei isolated from peat.  FEMS Microbiol. Lett. 2008, 287, 236–242. [Google Scholar]
12.
Kwon SJ, Lee J, Lee HS. Metabolic changes of the acetogen Clostridium sp. AWRP through adaptation to acetate challenge.  Front. Microbiol. 2022, 13, 982442. [Google Scholar]
13.
Hwang JH, Kim HJ, Kim S, Lee Y, Shin Y, Choi S, et al. Positive effect of phasin in biohydrogen production of non polyhydroxybutyrate-producing Clostridium acetobutylicum ATCC 824.  Bioresour. Tech. 2024, 395, 130355. [Google Scholar]
14.
Wu Y-D, Xue C, Chen L-J, Yuan W-J, Bai F-W. Improvements of metabolites tolerance in Clostridium acetobutylicum by micronutrient zinc supplementation.  Biotech. Bioproc. E. 2016, 21, 60–67. [Google Scholar]
15.
Bankar SB, Jurgens G, Survase SA, Ojamo H, Granström T. Genetic engineering of Clostridium acetobutylicum to enhance isopropanol-butanol-ethanol production with an integrated DNA-technology approach.  Renewable Energy 2015, 83, 1076–1083. [Google Scholar]
16.
Dai Z, Dong H, Zhu Y, Zhang Y, Li Y, Ma Y. Introducing a single secondary alcohol dehydrogenase into butanol-tolerant Clostridium acetobutylicum Rh8 switches ABE fermentation to high level IBE fermentation.  Biotech. Biofuels 2012, 5, 44. [Google Scholar]
17.
Lee J, Jang Y-S, Choi SJ, Im JA, Song H, Cho JH, et al. Metabolic engineering of Clostridium acetobutylicum ATCC 824 for isopropanol-butanol-ethanol fermentation.  Appl. Environ. Microbiol. 2012, 78, 1416–1423. [Google Scholar]
18.
Zhang J, Zong W, Hong W, Zhang Z-T, Wang Y. Exploiting endogenous CRISPR-Cas system for multiplex genome editing in Clostridium tyrobutyricum and engineer the strain for high-level butanol production.  Metab. Eng. 2018, 47, 49–59. [Google Scholar]
19.
Li T, Zhang C, Yang K-L, He J. Unique genetic cassettes in a Thermoanaerobacterium contribute to simultaneous conversion of cellulose and monosugars into butanol.  Sci. Adv. 2018, 4, e1701475. [Google Scholar]
20.
Jiménez-Bonilla P, Wang Y. In situ biobutanol recovery from clostridial fermentations: a critical review.  Crit. Rev. Biotech. 2018, 38, 469–482. [Google Scholar]
21.
De Gérando HM, Fayolle-Guichard F, Rudant L, Millah S, Monot F, Ferreira NL, et al. Improving isopropanol tolerance and production of Clostridium beijerinckii DSM 6423 by random mutagenesis and genome shuffling.  Appl. Microbiol. Biotech. 2016, 100, 5427–5436. [Google Scholar]
22.
Youn SH, Lee KM, Kim K-Y, Lee S-M, Woo HM, Um Y. Effective isopropanol–butanol (IB) fermentation with high butanol content using a newly isolated Clostridium sp. A1424.  Biotech. Biofuels 2016, 9, 230. [Google Scholar]
23.
Yang S, Giannone RJ, Dice L, Yang ZK, Engle NL, Tschaplinski TJ, et al. Clostridium thermocellum ATCC27405 transcriptomic, metabolomic and proteomic profiles after ethanol stress.  BMC Genom. 2012, 13, 336. [Google Scholar]
24.
Tolonen AC, Zuroff TR, Mohandass R, Boutard M, Cerisy T, Curtis WR. Physiology, genomics, and pathway engineering of an ethanol-tolerant strain of Clostridium phytofermentans.  Appl. Environ. Microbiol. 2015, 81, 5440–5448. [Google Scholar]
25.
Zhu Y, Yang ST. Adaptation of Clostridiumtyrobutyricum for Enhanced Tolerance to Butyric Acid in a Fibrous‐Bed Bioreactor.  Biotech. Progr. 2003, 19, 365–372. [Google Scholar]
26.
Wen Z, Ledesma-Amaro R, Lin J, Jiang Y, Yang S. Improved n-butanol production from Clostridium cellulovorans by integrated metabolic and evolutionary engineering.  Appl. Environ. Microbiol. 2019, 85, e02560-18. [Google Scholar]
27.
Lin PP, Mi L, Morioka AH, Yoshino KM, Konishi S, Xu SC, et al. Consolidated bioprocessing of cellulose to isobutanol using Clostridium thermocellum.  Metab. Eng. 2015, 31, 44–52. [Google Scholar]
28.
Higashide W, Li Y, Yang Y, Liao JC. Metabolic engineering of Clostridium cellulolyticum for production of isobutanol from cellulose.  Appl. Environ. Microbiol. 2011, 77, 2727–2733. [Google Scholar]
29.
Singh S, Cheng G, Sathitsuksanoh N, Wu D, Varanasi P, George A, et al. Comparison of different biomass pretreatment techniques and their impact on chemistry and structure.  Front. Energy Res. 2015, 2, 62. [Google Scholar]
30.
Mankar AR, Pandey A, Modak A, Pant KJBT. Pretreatment of lignocellulosic biomass: A review on recent advances.  Bioresour. Technol. 2021, 334, 125235. [Google Scholar]
31.
Liao Z, Guo X, Hu J, Suo Y, Fu H, Wang J. The significance of proline on lignocellulose-derived inhibitors tolerance in Clostridium acetobutylicum ATCC 824.  Bioresour. Tech. 2019, 272, 561–569. [Google Scholar]
32.
Ujor V, Agu CV, Gopalan V, Ezeji TC. Allopurinol-mediated lignocellulose-derived microbial inhibitor tolerance by Clostridium beijerinckii during acetone–butanol–ethanol (ABE) fermentation.  Appl. Microbiol. Biotech. 2015, 99, 3729–3740. [Google Scholar]
33.
Ezeji T, Qureshi N, Blaschek HP. Butanol production from agricultural residues: impact of degradation products on Clostridium beijerinckii growth and butanol fermentation.  Biotech. Bioeng. 2007, 97, 1460–1469. [Google Scholar]
34.
Yao D, Dong S, Wang P, Chen T, Wang J, Yue Z-B, Wang Y. Robustness of Clostridium saccharoperbutylacetonicum for acetone-butanol-ethanol production: Effects of lignocellulosic sugars and inhibitors.  Fuel 2017, 208, 549–557. [Google Scholar]
35.
Liu J, Lin Q, Chai X, Luo Y, Guo T. Enhanced phenolic compounds tolerance response of Clostridium beijerinckii NCIMB 8052 by inactivation of Cbei_3304.  Microb. Cell Fact. 2018, 17, 35. [Google Scholar]
36.
Cho DH, Lee YJ, Um Y, Sang B-I, Kim YH. Detoxification of model phenolic compounds in lignocellulosic hydrolysates with peroxidase for butanol production from Clostridium beijerinckii.  Appl. Microbiol. Biotech. 2009, 83, 1035–1043. [Google Scholar]
37.
Liu J, Liu Z, Chai X, Luo Y, Guo T, Ying H. Regulation of ρ-coumaric acid tolerance in Clostridium beijerinckii by disturbing the intracellular electron transport chain.  Process Biochem. 2018, 68, 43–52. [Google Scholar]
38.
Chen W-H, Zeng Y-R. Mathematical model to appraise the inhibitory effect of phenolic compounds derived from lignin for biobutanol production.  Bioresour. Tech. 2018, 261, 44–51. [Google Scholar]
39.
Lan EI, Liao JC. ATP drives direct photosynthetic production of 1-butanol in cyanobacteria. Proc. Natl. Acad. Sci.  2012 109, 6018–6023, . [Google Scholar]
40.
Zhang L, Nie X, Ravcheev DA, Rodionov DA, Sheng J, Gu Y, et al. Redox-responsive repressor Rex modulates alcohol production and oxidative stress tolerance in Clostridium acetobutylicum.  J. Bacteriol. 2014, 196, 3949–3963. [Google Scholar]
41.
Wang C, Xin F, Kong X, Zhao J, Dong W, Zhang W, et al. Enhanced isopropanol–butanol–ethanol mixture production through manipulation of intracellular NAD (P) H level in the recombinant Clostridium acetobutylicum XY16.  Biotech. Biofuels 2018, 11, 12. [Google Scholar]
42.
Wu Q, Zhu L, Xu Q, Huang H, Jiang L, Yang S-T. Tailoring the Oxidative Stress Tolerance of Clostridium tyrobutyricum CCTCC W428 by Introducing Trehalose Biosynthetic Capability.  J. Agric. Food Chem. 2017, 65, 8892–8901. [Google Scholar]
43.
Liao Z, Zhang Y, Luo S, Suo Y, Zhang S, Wang J. Improving cellular robustness and butanol titers of Clostridium acetobutylicum ATCC824 by introducing heat shock proteins from an extremophilic bacterium.  J. Biotech. 2017, 252, 1–10. [Google Scholar]
44.
Tao W, Dong H, Zhang Y, Cai Z, Li Y. Introducing transglutaminase with its precursor region into Clostridium acetobutylicum improves its tolerance to oxidative stress and solvent production.  Process Biochem. 2015, 50, 111–118. [Google Scholar]
45.
Kawasaki S, Sakai Y, Takahashi T, Suzuki I, Niimura Y. O2 and reactive oxygen species detoxification complex, composed of O2-responsive NADH: rubredoxin oxidoreductase-flavoprotein A2-desulfoferrodoxin operon enzymes, rubperoxin, and rubredoxin, in Clostridium acetobutylicum.  Appl. Environ. Microbiol. 2009, 75, 1021–1029. [Google Scholar]
46.
Al-Shorgani NKN, Kalil MS, Yusoff WMW, Hamid AA. Biobutanol production by a new aerotolerant strain of Clostridium acetobutylicum YM1 under aerobic conditions.  Fuel 2015, 158, 855–863. [Google Scholar]
47.
Hillmann F, Fischer RJ, Saint‐Prix F, Girbal L, Bahl H. PerR acts as a switch for oxygen tolerance in the strict anaerobe Clostridium acetobutylicum.  Mol. Microbiol. 2008, 68, 848–860. [Google Scholar]
48.
Liu Z-Y, Yao X-Q, Zhang Q, Liu Z, Wang Z-J, Zhang Y-Y, et al. Modulation of the acetone/butanol ratio during fermentation of corn stover-derived hydrolysate by Clostridium beijerinckii strain NCIMB 8052.  Appl. Environ. Microbiol. 2017, 83, e03386–03316. [Google Scholar]
49.
Kang M-K, Nielsen J. Biobased production of alkanes and alkenes through metabolic engineering of microorganisms.  J. Indust. Microbiol. Biotech. 2017, 44, 613–622. [Google Scholar]
50.
Zhu L, Dong H, Zhang Y, Li Y. Engineering the robustness of Clostridium acetobutylicum by introducing glutathione biosynthetic capability.  Metab. Eng. 2011, 13, 426–434. [Google Scholar]
51.
Lin Z, Liu H, Yan X, Zhou Y, Cheng K, Zhang J. High-efficiency acetone-butanol-ethanol production and recovery in non-strict anaerobic gas-stripping fed-batch fermentation.  Appl. Microbiol. Biotech. 2017, 101, 8029–8039. [Google Scholar]
52.
Wu P, Wang G, Wang G, Børresen BT, Liu H, Zhang J. Butanol production under microaerobic conditions with a symbiotic system of Clostridium acetobutylicum and Bacillus cereus.  Microb. Cell Fact. 2016, 15, 8. [Google Scholar]
53.
Mai S, Wang G, Wu P, Gu C, Liu H, Zhang J, et al. Interactions between Bacillus cereus CGMCC 1.895 and Clostridium beijerinckii NCIMB 8052 in coculture for butanol production under nonanaerobic conditions.  Biotech. Appl. Biochem. 2017, 64, 719–726. [Google Scholar]
54.
Luo H, Ge L, Zhang J, Zhao Y, Ding J, Li Z, et al. Enhancing butanol production under the stress environments of co-culturing Clostridium acetobutylicum/Saccharomyces cerevisiae integrated with exogenous butyrate addition.  PloS ONE 2015, 10, e0141160. [Google Scholar]
55.
Du Y, Zou W, Zhang K, Ye G, Yang J. Advances and applications of Clostridium co-culture systems in biotechnology.  Front. Microbiol. 2020, 11, 560223. [Google Scholar]
56.
Zhao, X, Condruz, S, Chen, J, Jolicoeur, M. A quantitative metabolomics study of high sodium response in Clostridium acetobutylicum ATCC 824 acetone-butanol-ethanol (ABE) fermentation.  Sci. Rep. 2016, 6, 28307. [Google Scholar]
57.
Zabihi R, Mowla D, Karimi G. Production of biosolvents and acids by salinity-adapted strain of Clostridium acetobutylicum: Effects of salt and molasses concentrations.  J. Serb. Chem. Soc. 2018, 83, 411–423. [Google Scholar]
58.
Lee JW, Na D, Park JM, Lee J, Choi S, Lee SY. Systems metabolic engineering of microorganisms for natural and non-natural chemicals.  Nat. Chem. Biol. 2012, 8, 536. [Google Scholar]
59.
Liu W, Zhang X-Z, Zhang Z, Zhang Y-HP. Engineering of Clostridium phytofermentans endoglucanase Cel5A for improved thermostability.  Appl. Environ. Microbiol. 2010, 76, 4914–4917. [Google Scholar]
60.
Sandoval-Espinola WJ, Makwana ST, Chinn MS, Thon MR, Azcárate-Peril MA, Bruno-Barcena JM. Comparative phenotypic analysis and genome sequence of Clostridium beijerinckii SA-1, an offspring of NCIMB 8052.  Microbiology 2013, 159, 2558–2570. [Google Scholar]
61.
Patankar S, Dudhane A, Paradh A, Patil S. Improved bioethanol production using genome-shuffled Clostridium ragsdalei (DSM 15248) strains through syngas fermentation.  Biofuels 2018, 12, 81–89. [Google Scholar]
62.
Vasylkivska M, Branska B, Sedlar K, Jureckova K, Provaznik I, Patakova P. Phenotypic and genomic analysis of Clostridium beijerinckii NRRL B-598 mutants with increased butanol tolerance.  Front. Bioeng. Biotech. 2020, 8, 598392. [Google Scholar]
63.
Jain, M.K, Beacom, D, Datta, R. Mutant strain of C. acetobutylicum and process for making butanol. US Patent 5,192,673. May 9th, 1993.
64.
Gao X, Zhao H, Zhang G, He K, Jin Y. Genome shuffling of Clostridium acetobutylicum CICC 8012 for improved production of acetone–butanol–ethanol (ABE).  Curr. Microbiol. 2012, 65, 128–132. [Google Scholar]
65.
Mermelstein LD, Welker NE, Bennett GN, Papoutsakis ET. Expression of cloned homologous fermentative genes in Clostridium acetobutylicum ATCC 824.  Nat. Biotech. 1992, 10, 190. [Google Scholar]
66.
Moon HG, Jang Y-S, Cho C, Lee J, Binkley R, Lee SY. One hundred years of clostridial butanol fermentation.  FEMS Microbiol. Lett. 2016, 363, fnw001. [Google Scholar]
67.
Xu T, Li Y, Shi Z, Hemme CL, Li Y, Zhu Y, et al. Efficient genome editing in Clostridium cellulolyticum via CRISPR-Cas9 nickase.  Appl. Environ. Microbiol. 2015, 81, 4423–4431. [Google Scholar]
68.
Wang Y, Zhang Z-T, Seo S-O, Lynn P, Lu T, Jin Y-S, et al. Bacterial genome editing with CRISPR-Cas9: deletion, integration, single nucleotide modification, and desirable “clean” mutant selection in Clostridium beijerinckii as an example.  ACS Synth. Biol. 2016, 5, 721–732. [Google Scholar]
69.
Li Q, Seys FM, Minton NP, Yang J, Jiang Y, Jiang W, et al. CRISPR‐Cas9D10A nickase‐assisted base editing in solvent producer Clostridium beijerinckii.  Biotech. Bioeng. 2019, 113, 1475–1483. [Google Scholar]
70.
Zhang J, Hong W, Zong W, Wang P, Wang Y. Markerless genome editing in Clostridium beijerinckii using the CRISPR-Cpf1 system.  J. Biotech. 2018, 284, 27–30. [Google Scholar]
71.
Patinios C, de Vries ST, Diallo M, Lanza L, Verbrugge PL, López-Contreras AM, et al. Multiplex genome engineering in Clostridium beijerinckii NCIMB 8052 using CRISPR-Cas12a.  Sci. Rep. 2023, 13, 10153. [Google Scholar]
72.
Wang Y, Zhang ZT, Seo SO, Lynn P, Lu T, Jin YS, et al. Gene transcription repression in Clostridium beijerinckii using CRISPR‐dCas9.  Biotech. Bioeng. 2016, 113, 2739–2743. [Google Scholar]
73.
Woolston BM, Emerson DF, Currie DH, Stephanopoulos G. Rediverting carbon flux in Clostridium ljungdahlii using CRISPR interference (CRISPRi).  Metab. Eng. 2018, 48, 243–253. [Google Scholar]
74.
Rostain W, Zaplana T, Boutard M, Baum C, Tabuteau S, Sanitha M, et al. Tuning of Gene Expression in Clostridium phytofermentans Using Synthetic Promoters and CRISPRi.  ACS Synth. Biol. 2022, 11, 4077–4088. [Google Scholar]
75.
Liu X, Gallay C, Kjos M, Domenech A, Slager J, van Kessel SP, et al. High‐throughput CRISPRi phenotyping identifies new essential genes in Streptococcus pneumoniae.  Mol. Syst. Biol. 2017, 13, 931. [Google Scholar]
76.
Joseph RC, Sandoval NR. Single and multiplexed gene repression in solventogenic Clostridium via Cas12a-based CRISPR interference.  Synth. Syst. Biotech. 2023, 8, 148–156. [Google Scholar]
77.
La Russa MF, Qi LS. The new state of the art: Cas9 for gene activation and repression.  Mol. Cell. Biol. 2015, 35, 3800–3809. [Google Scholar]
78.
Pyne ME, Bruder MR, Moo-Young M, Chung DA, Chou CP. Harnessing heterologous and endogenous CRISPR-Cas machineries for efficient markerless genome editing in Clostridium.  Sci. Rep. 2016, 6, 25666. [Google Scholar]
79.
Hegge JW, Swarts DC, Chandradoss SD, Cui TJ, Kneppers J, Jinek M, et al. DNA-guided DNA cleavage at moderate temperatures by Clostridium butyricum Argonaute.  Nucleic Acid Res. 2019, 47, 5809–5821. [Google Scholar]
80.
Liyanage H, Young M, Kashket E. Butanol tolerance of Clostridium beijerinckii NCIMB 8052 associated with down-regulation of gldA by antisense RNA.  J. Mol. Microbiol. Biotech. 2000, 2, 87–93. [Google Scholar]
81.
Tomas CA, Beamish J, Papoutsakis ET. Transcriptional analysis of butanol stress and tolerance in Clostridium acetobutylicum.  J. Bacteriol. 2004, , 186, 2006–2018. [Google Scholar]
82.
Atmadjaja AN, Holby V, Harding AJ, Krabben P, Smith HK, Jenkinson ER. CRISPR-Cas, a highly effective tool for genome editing in Clostridium saccharoperbutylacetonicum N1-4 (HMT).  FEMS Microbiol. Lett. 2019, 366, fnz059. [Google Scholar]
83.
Jiménez-Bonilla P, Zhang J, Wang Y, Blersch D, de-Bashan L-E, Guo L, et al. Enhancing the tolerance of Clostridium saccharoperbutylacetonicum to lignocellulosic-biomass-derived inhibitors for efficient biobutanol production by overexpressing efflux pumps genes from Pseudomonas putida.  Bioresour. Tech. 2020, 312, 123532. [Google Scholar]
84.
Gu Y, Feng J, Zhang Z-T, Wang S, Guo L, Wang Y, et al. Curing the endogenous megaplasmid in Clostridium saccharoperbutylacetonicum N1-4 (HMT) using CRISPR-Cas9 and preliminary investigation of the role of the plasmid for the strain metabolism.  Fuel 2019, 236, 1559–1566. [Google Scholar]
85.
Feng J, Zhang J, Wang P, Jimenez-Bonilla P, Gu Y, Zhou J, et al. Renewable Fatty Acid Ester Production in Clostridium.  BioRxiv 2020, 0, 014746. doi:10.1101/2020.03.29.014746. [Google Scholar]
86.
Jiménez-Bonilla P, Feng J, Wang S, Zhang J, Wang Y, Blersch D, et al. Identification and Investigation of Autolysin Genes in Clostridium saccharoperbutylacetonicum Strain N1-4 for Enhanced Biobutanol Production.  Appl. Environ. Microbiol. 2021, 87, e02442–02420. [Google Scholar]
87.
Raganati F, Procentese A, Olivieri G, Russo ME, Gotz P, Salatino P, et al. Butanol production by Clostridium acetobutylicum in a series of packed bed biofilm reactors.  Chem. Eng. Sci. 2016, 152, 678–688. [Google Scholar]
88.
Qureshi N, Karcher P, Cotta M, Blaschek HP. High-productivity continuous biofilm reactor for butanol production.  Appl. Biochem. Biotech. 2004, 114, 713–721. [Google Scholar]
89.
Liu D, Chen Y, Ding F-Y, Zhao T, Wu J-L, Guo T, et al. Biobutanol production in a Clostridium acetobutylicum biofilm reactor integrated with simultaneous product recovery by adsorption.  Biotech. Biofuels 2014, 7, 5. [Google Scholar]
90.
Zhou W, Liu J, Fan S, Xiao Z, Qiu B, Wang Y, et al. Biofilm immobilization of Clostridium acetobutylicum on particulate carriers for acetone-butanol-ethanol (ABE) production.  Biores. Tech. Rep. 2018, 3, 211–217. [Google Scholar]
91.
Zhuang W, Liu X, Yang J, Wu J, Zhou J, Chen Y, et al. Immobilization of Clostridium acetobutylicum onto natural textiles and its fermentation properties.  Microb. Biotech. 2017, 10, 502–512. [Google Scholar]
92.
Zhuang W, Yang J, Wu J, Liu D, Zhou J, Chen Y, et al. Extracellular polymer substances and the heterogeneity of Clostridium acetobutylicum biofilm induced tolerance to acetic acid and butanol.  RSC Adv. 2016, 6, 33695–33704. [Google Scholar]
93.
Chin W-C, Lin K-H, Liu C-C, Tsuge K, Huang C-C. Improved n-butanol production via co-expression of membrane-targeted tilapia metallothionein and the clostridial metabolic pathway in Escherichia coli.  BMC Biotech. 2017, 17, 36. [Google Scholar]
94.
Ruttkay-Nedecky B, Nejdl L, Gumulec J, Zitka O, Masarik M, Eckschlager T, et al. The role of metallothionein in oxidative stress.  Int. J. Mol. Sci. 2013, 14, 6044–6066. [Google Scholar]
95.
Liao C, Seo S-O, Celik V, Liu H, Kong W, Wang Y, et al. Integrated, systems metabolic picture of acetone-butanol-ethanol fermentation by Clostridium acetobutylicum.  Proc. Natl. Acad. Sci. 2015, 112, 8505–8510. [Google Scholar]
96.
Fischer RJ, Helms J, Dürre P. Cloning, sequencing, and molecular analysis of the sol operon of Clostridium acetobutylicum, a chromosomal locus involved in solventogenesis.  J. Bacteriol. 1993, 175, 6959–6969. [Google Scholar]
97.
Lee SY, Park JH, Jang SH, Nielsen LK, Kim J, Jung KS. Fermentative butanol production by Clostridia.  Biotech. Bioeng. 2008, 101, 209–228. [Google Scholar]
98.
Xu M, Zhao J, Yu L, Tang I-C, Xue C, Yang S-T. Engineering Clostridium acetobutylicum with a histidine kinase knockout for enhanced n-butanol tolerance and production.  Appl. Microbiol. Biotech. 2015, 99, 1011–1022. [Google Scholar]
99.
Jia K, Zhang Y, Li Y. Identification and characterization of two functionally unknown genes involved in butanol tolerance of Clostridium acetobutylicum.  PloS ONE 2012, 7, e38815. [Google Scholar]
100.
Żwirowski S, Kłosowska A, Obuchowski I, Nillegoda NB, Piróg A, Ziętkiewicz S, et al. Hsp70 displaces small heat shock proteins from aggregates to initiate protein refolding.  EMBO J. 2017, 36, 783–796. [Google Scholar]
101.
Horwich AL, Farr GW, Fenton WA. GroEL−GroES-mediated protein folding.  Chem. Rev. 2006, 106, 1917–1930. [Google Scholar]
102.
Mann MS, Dragovic Z, Schirrmacher G, Lütke-Eversloh T. Over-expression of stress protein-encoding genes helps Clostridium acetobutylicum to rapidly adapt to butanol stress.  Biotech. Lett. 2012, 34, 1643–1649. [Google Scholar]
103.
Luan G, Dong H, Zhang T, Lin Z, Zhang Y, Li Y, et al. Engineering cellular robustness of microbes by introducing the GroESL chaperonins from extremophilic bacteria.  J. Biotech. 2014, 178, 38–40. [Google Scholar]
104.
Hillmann F, Fischer R-J, Bahl H. The rubrerythrin-like protein Hsp21 of Clostridium acetobutylicum is a general stress protein.  Arch. Microbiol. 2006, 185, 270. [Google Scholar]
105.
Wang Q, Venkataramanan KP, Huang H, Papoutsakis ET, Wu CH.  Transcription factors and genetic circuits orchestrating the complex, multilayered response of Clostridium acetobutylicum to butanol and butyrate stress.  BMC Syst. Biol. 2013, 7, 120. [Google Scholar]
106.
Suo Y, Luo S, Zhang Y, Liao Z, Wang J. Enhanced butyric acid tolerance and production by Class I heat shock protein-overproducing Clostridium tyrobutyricum ATCC 25755.  J. Indust. Microbiol. Biotech. 2017, 44, 1145–1156. [Google Scholar]
107.
Anes J, McCusker MP, Fanning S, Martins M. The ins and outs of RND efflux pumps in Escherichia coli.  Front. Microbiol. 2015, 6, 587. [Google Scholar]
108.
Nikaido H. RND transporters in the living world.  Res. Microbiol. 2018, 169, 363–371. [Google Scholar]
109.
Ramos J-L, Sol Cuenca M, Molina-Santiago C, Segura A, Duque E, Gómez-García MR, Udaondo Z, Roca A. Mechanisms of solvent resistance mediated by interplay of cellular factors in Pseudomonas putida.  FEMS Microbiol. Rev. 2015, 39, 555–566. [Google Scholar]
110.
Nikaido H, Takatsuka Y. Mechanisms of RND multidrug efflux pumps.  BBA Proteins Proteom. 2009, 1794, 769–781. [Google Scholar]
111.
Dunlop MJ, Dossani ZY, Szmidt HL, Chu HC, Lee TS, Keasling JD, et al. Engineering microbial biofuel tolerance and export using efflux pumps.  Mol. Syst. Biol. 2011, 7, 487. [Google Scholar]
112.
Fisher MA, Boyarskiy S, Yamada MR, Kong N, Bauer S, Tullman-Ercek D. Enhancing tolerance to short-chain alcohols by engineering the Escherichia coli AcrB efflux pump to secrete the non-native substrate n-butanol.  ACS Synth. Biol. 2013, 3, 30–40. [Google Scholar]
113.
Turner WJ, Dunlop MJ. Trade-offs in improving biofuel tolerance using combinations of efflux pumps.  ACS Synth. Biol. 2014, 4, 1056–1063. [Google Scholar]
114.
Kieboom J, Dennis JJ, Zylstra GJ, De Bont JA. Active Efflux of Organic Solvents byPseudomonas putida S12 Is Induced by Solvents.  J. Bacteriol. 1998, 180, 6769–6772. [Google Scholar]
115.
Bui LM, Lee JY, Geraldi A, Rahman Z, Lee JH, Kim SC. Improved n-butanol tolerance in Escherichia coli by controlling membrane related functions.  J. Biotech. 2015, 204, 33–44. [Google Scholar]
116.
Tan Z, Yoon JM, Nielsen DR, Shanks JV, Jarboe LR. Membrane engineering via trans unsaturated fatty acids production improves Escherichia coli robustness and production of biorenewables.  Metab. Eng. 2016, 35, 105–113. [Google Scholar]
117.
Sandoval NR, Papoutsakis ET. Engineering membrane and cell-wall programs for tolerance to toxic chemicals: Beyond solo genes.  Curr. Opin. Microbiol. 2016, 33, 56–66. [Google Scholar]
118.
Huffer S, Clark ME, Ning JC, Blanch HW, Clark DS. The role of alcohols in growth, lipid composition, and membrane fluidity of yeast, bacteria, and archaea.  Appl. Environ. Microbiol. 2011, 77, 6400–6408. [Google Scholar]
119.
Timmons MD, Knutson BL, Nokes SE, Strobel HJ, Lynn BC. Analysis of composition and structure of Clostridium thermocellum membranes from wild-type and ethanol-adapted strains.  Appl. Microbiol. Biotech. 2009, 82, 929–939. [Google Scholar]
120.
Tian B, Guan Z, Goldfine H. An ethanolamine-phosphate modified glycolipid in Clostridium acetobutylicum that responds to membrane stress. BBA-Mol.  Cell Biol. Lipids 2013, 1831, 1185–1190. [Google Scholar]
121.
Kolek J, Patáková P, Melzoch K, Sigler K, Řezanka T. Changes in membrane plasmalogens of Clostridium pasteurianum during butanol fermentation as determined by lipidomic analysis.  PLoS ONE 2015, 10, e0122058. [Google Scholar]
122.
Van Der Westhuizen A, Jones DT, Woods DR. Autolytic activity and butanol tolerance of Clostridium acetobutylicum.  Appl. Environ. Microbiol. 1982, 44, 1277–1281. [Google Scholar]
123.
Webster JR, Reid SJ, Jones DT, Woods DR. Purification and characterization of an autolysin from Clostridium acetobutylicum.  Appl. Environ. Microbiol. 1981, 41, 371–374. [Google Scholar]
124.
Allcock ER, Reid SJ, Jones DT, Woods DR.  Autolytic activity and an autolysis-deficient mutant of Clostridium acetobutylicum. Appl. Environ. Microbiol. , 1981, 42. 929–935 [Google Scholar]
125.
Croux C, Canard B, Goma G, Soucaille P. Autolysis of Clostridium acetobutylicum ATCC 824.  Microbiology 1992, 138, 861–869. [Google Scholar]
126.
Yoshino S, Ogata S, Hayashida S. Some properties of autolysin of Clostridium saccharoperbutylacetonicum.  Agr. Biol. Chem. 1982, 46, 1243–1248. [Google Scholar]
127.
Ogata S, Hongo M. Lysis induced by sodium ion and its relation to lytic enzyme systems in Clostridium saccharoperbutylacetonicum.  Microbiology 1974, 81, 315–323. [Google Scholar]
128.
Yang L, Bao G, Zhu Y, Dong H, Zhang Y, Li Y. Discovery of a novel gene involved in autolysis of Clostridium cells.  Protein Cell 2013, 4, 467–474. [Google Scholar]
129.
Liu Z, Qiao K, Tian L, Zhang Q, Liu Z-Y, Li F-L. Spontaneous large-scale autolysis in Clostridium acetobutylicum contributes to generation of more spores.  Front. Microbiol. 2015, 6, 950. [Google Scholar]
130.
Zhang Y. Detoxification of Lignocellulose-derived Microbial Inhibitory Compounds by Clostridium beijerinckii NCIMB 8052 during Acetone-Butanol-Ethanol Fermentation. Dissertation for Doctoral Degree; The Ohio State University: Columbus, OH 43210, USA; 2013.
131.
Frank C, Schwarz U, Matthies C, Drake HL. Metabolism of aromatic aldehydes as cosubstrates by the acetogen Clostridium formicoaceticum.  Arch. Microbiol. 1998, 170, 427–434. [Google Scholar]
132.
Chamkha M, Garcia J-L, Labat M. Metabolism of cinnamic acids by some Clostridiales and emendation of the descriptions of Clostridium aerotolerans, Clostridium celerecrescens and Clostridium xylanolyticum.  Int. J. Systemat. Evolutionary Microbiol. 2001, 51, 2105–2111. [Google Scholar]
133.
Schmid, R, Schmidt-Dannert, C. Biotechnollogy. An ilustrated primer; Wiley-VCH: Weinheim, Germany; 2016.
134.
Horgan RP, Kenny LC. ‘Omic’technologies: genomics, transcriptomics, proteomics and metabolomics.  Obstetrician Gynaecologist 2011, 13, 189–195. [Google Scholar]
135.
Alsaker KV, Paredes C, Papoutsakis, E.T. 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.  Biotech. Bioeng. 2010, 105, 1131–1147. [Google Scholar]
Creative Commons

© 2024 by the authors; licensee SCIEPublish, SCISCAN co. Ltd. This article is an open access article distributed under the CC BY license (https://creativecommons.org/licenses/by/4.0/).