Abstract
Most current biotechnology industries are based on batch or fed-batch fermentation processes, which often show low productivity and high production costs compared to chemical processes. To increase the economic competitiveness of biological processes, continuous fermentation technologies are being developed that offer significant advantages in comparison with batch/fed-batch fermentation processes, including: (1) removal of potential substrates and product inhibition, (2) prolonging the microbial exponential growth phase and enhancing productivity, and (3) avoiding repeated fermentation preparation and lowering operation and installation costs. However, several key challenges should be addressed for the industrial application of continuous fermentation processes, including (1) contamination of the fermentation system, (2) degeneration of strains, and (3) relatively low product titer. In this study, we reviewed and discussed metabolic engineering and synthetic biology strategies to address these issues.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Clomburg J M, Crumbley A M, Gonzalez R. Industrial biomanufacturing: the future of chemical production. Science, 2017, 355(6320): aag0804
Formenti L R, Norregaard A, Bolic A, Hernandez D Q, Hagemann T, Heins A L, Larsson H, Mears L, Mauricio-Iglesias M, Krühne U, Gernaey K V. Challenges in industrial fermentation technology research. Biotechnology Journal, 2014, 9(6): 727–738
Gu Y, Jiang Y, Wu H, Liu X, Li Z, Li J, Xiao H, Shen Z, Dong H, Yang Y, Li Y, Jiang W, Yang S. Economical challenges to microbial producers of butanol: feedstock, butanol ratio and titer. Biotechnology Journal, 2011, 6(11): 1348–1357
Li T, Chen X B, Chen J C, Wu Q, Chen G Q. Open and continuous fermentation: products, conditions and bioprocess economy. Biotechnology Journal, 2014, 9(12): 1503–1511
Verbelen P J, De Schutter D P, Delvaux F, Verstrepen K J, Delvaux F R. Immobilized yeast cell systems for continuous fermentation applications. Biotechnology Letters, 2006, 28(19): 1515–1525
Talebnia F, Taherzadeh M J. In situ detoxification and continuous cultivation of dilute-acid hydrolyzate to ethanol by encapsulated S. cerevisiae. Journal of Biotechnology, 2006, 125(3): 377–384
Mussatto S I, Dragone G, Guimaraes P M, Silva J P, Carneiro L M, Roberto I C, Vicente A, Domingues L, Teixeira J A. Technological trends, global market, and challenges of bioethanol production. Biotechnology Advances, 2010, 28(6): 817–830
Ghose T K, Tyagi R D. Rapid ethanol fermentation of cellulose hydrolysate. I. Batch versus continuous systems. Biotechnology and Bioengineering, 1979, 21(8): 1387–1400
Ding S F, Tan T W. L-lactic acid production by Lactobacillus casei fermentation using different fed-batch feeding strategies. Process Biochemistry, 2006, 41(6): 1451–1454
Chen Y, Liu Q, Zhou T, Li B, Yao S, Li A, Wu J, Ying H. Ethanol production by repeated batch and continuous fermentations by Saccharomyces cerevisiae immobilized in a fibrous bed bioreactor. Journal of Microbiology and Biotechnology, 2013, 23(4): 511–517
Yue H T, Ling C, Yang T, Chen X B, Chen Y L, Deng H T, Wu Q, Chen J C, Chen G Q. A seawater-based open and continuous process for polyhydroxyalkanoates production by recombinant Halomonas campaniensis LS21 grown in mixed substrates. Biotechnology for Biofuels, 2014, 7(1): 1–12
Mitsumasu K, Liu Z S, Tang Y Q, Akamatsu T, Taguchi H, Kida K. Development of industrial yeast strain with improved acid- and thermo-tolerance through evolution under continuous fermentation conditions followed by haploidization and mating. Journal of Bioscience and Bioengineering, 2014, 118(6): 689–695
Branyik T, Vicente A, Cruz J M, Teixeira J. Continuous primary beer fermentation with brewing yeast immobilized on spent grains. Journal of the Institute of Brewing, 2002, 108(4): 410–415
Wang J, Lihan Z I, Bai F. Co-production of ethanol and yeast during continuous fermentation using self-flocculating fusant SPSC01. Journal of Chemical Industry and Engineering, 2004, 55(6): 1024–1027 (in Chinese)
Ren N Q, Li J Z, Li B K, Wang Y, Liu S R. Biohydrogen production from molasses by anaerobic fermentation with a pilot-scale bioreactor system. International Journal of Hydrogen Energy, 2006, 31(15): 2147–2157
Gao M T, Koide M, Gotou R, Takanashi H, Hirata M, Hano T. Development of a continuous electrodialysis fermentation system for production of lactic acid by Lactobacillus rhamnosus. Process Biochemistry, 2004, 40(3–4): 1033–1036
Hirao T, Nakano T, Azuma T, Sugimoto M, Nakanishi T. L-Lysine production in continuous culture of an L-lysine hyperproducing mutant of Corynebacterium glutamicum. Applied Microbiology and Biotechnology, 2004, 32: 269–273
Yan Q, Zheng P, Tao S T, Dong J J. Fermentation process for continuous production of succinic acid in a fibrous bed bioreactor. Biochemical Engineering Journal, 2014, 91: 92–98
Yen H W, Li R J, Ma T W. The development process for a continuous acetone-butanol-ethanol (ABE) fermentation by immobilized Clostridium acetobutylicum. Journal of the Taiwan Institute of Chemical Engineers, 2011, 42(6): 902–907
Chatzifragkou A, Papanikolaou S, Dietz D, Doulgeraki A I, Nychas G J, Zeng A P. Production of 1,3-propanediol by Clostridium butyricum growing on biodiesel-derived crude glycerol through a non-sterilized fermentation process. Applied Microbiology and Biotechnology, 2011, 91(1): 101–112
Huang W C, Ramey D E, Yang S T. Continuous production of butanol by Clostridium acetobutylicum immobilized in a fibrous bed bioreactor. Applied Biochemistry and Biotechnology, 2004, 113–116(1–3): 887–898
Alfenore S, Molina Jouve C, Guillouet S E, Uribelarrea J L, Goma G, Benbadis L. Improving ethanol production and viability of Saccharomyces cerevisiae by a vitamin feeding strategy during fed-batch process. Applied Microbiology and Biotechnology, 2002, 60(1–2): 67–72
Tan D, Xue Y S, Aibaidula G, Chen G Q. Unsterile and continuous production of polyhydroxybutyrate by Halomonas TD01. Bioresource Technology, 2011, 102(17): 8130–8136
Nishie M, Nagao J, Sonomoto K. Antibacterial peptides “bacteriocins”: an overview of their diverse characteristics and applications. Biocontrol Science, 2012, 17(1): 1–16
Kivistö A, Santala V, Karp M. Non-sterile process for biohydrogen and 1,3-propanediol production from raw glycerol. International Journal of Hydrogen Energy, 2013, 38(27): 11749–11755
Saithong P, Nakamura T, Shima J. Prevention of bacterial contamination using acetate-tolerant Schizosaccharomyces pombe during bioethanol production from molasses. Journal of Bioscience and Bioengineering, 2009, 108(3): 216–219
Sanchez C. Bacterial evolution: phage resistance comes at a cost. Nature Reviews Microbiology, 2011, 9(6): 398–399
Scanlan P D, Buckling A, Hall A R. Experimental evolution and bacterial resistance: (co)evolutionary costs and trade-offs as opportunities in phage therapy research. Bacteriophage, 2015, 5(2): e1050153
Xiao Y, Bowen C H, Liu D, Zhang F. Exploiting nongenetic cell-to-cell variation for enhanced biosynthesis. Nature Chemical Biology, 2016, 12(5): 339–344
Smith A S, Rawlings D E. The poison-antidote stability system of the broad-host-range Thiobacillus ferrooxidans plasmid pTF-FC2. Molecular Microbiology, 2010, 26(5): 961–970
Nilsson J, Skogman S G. Stabilization of Escherichia coli tryptophan-production vectors in continuous cultures: a comparison of three different systems. Nature Biotechnology, 1986, 4(10): 901–903
Jojima T, Fujii M, Mori E, Inui M, Yukawa H. Engineering of sugar metabolism of Corynebacterium glutamicum for production of amino acid L-alanine under oxygen deprivation. Applied Microbiology and Biotechnology, 2010, 87(1): 159–165
Emmerling M, Bailey J E, Sauer U. Glucose catabolism of Escherichia coli strains with increased activity and altered regulation of key glycolytic enzymes. Metabolic Engineering, 1999, 1(2): 117–127
Katakura Y, Moukamnerd C, Harashima S, Kino-oka M. Strategy for preventing bacterial contamination by adding exogenous ethanol in solid-state semi-continuous bioethanol production. Journal of Bioscience and Bioengineering, 2011, 111(3): 343–345
Watanabe I, Nakamura T, Shima J. A strategy to prevent the occurrence of Lactobacillus strains using lactate-tolerant yeast Candida glabrata in bioethanol production. Journal of Industrial Microbiology & Biotechnology, 2008, 35(10): 1117–1122
Solomon E B, Okull D. Utilization of bacteriophage to control bacterial contamination in fermentation processes. US Patent, 20090104157A1, 2009-04-23
Tiquia S M, Davis D, Hadid H, Kasparian S, Ismail M, Sahly R, Shim J, Singh S, Murray K S. Halophilic and halotolerant bacteria from river waters and shallow groundwater along the Rouge River of southeastern Michigan. Environmental Technology, 2007, 28(3): 297–307
Chen G Q, Jiang X R. Next generation industrial biotechnology based on extremophilic bacteria. Current Opinion in Biotechnology, 2018, 50: 94–100
Zhang D X, Cheryan M. Direct fermentation of starch to lactic acid by Lactobacillus amylovorus. Biotechnology Letters, 1991, 13(10): 733–738
Zhang D X, Cheryan M. Starch to lactic acid in a continuous membrane bioreactor. Process Biochemistry, 1994, 29(2): 145–150
Meng W, Zhang Y, Ma L, Lu C, Xu P, Ma C, Gao C. Non-sterilized fermentation of 2,3-butanediol with seawater by metabolic engineered fast-growing Vibrio natriegens. Frontiers in Bioengineering and Biotechnology, 2022, 10: 955097
Linder T. Assimilation of alternative sulfur sources in fungi. World Journal of Microbiology & Biotechnology, 2018, 34(4): 51
Mandell D J, Lajoie M J, Mee M T, Takeuchi R, Kuznetsov G, Norville J E, Gregg C J, Stoddard B L, Church G M. Biocontainment of genetically modified organisms by synthetic protein design. Nature, 2015, 518(7537): 55–60
Johannes T W, Woodyer R D, Zhao H. Efficient regeneration of NADPH using an engineered phosphite dehydrogenase. Biotechnology and Bioengineering, 2007, 96(1): 18–26
Hung C L, Liu J H, Chiu W C, Huang S W, Hwang J K, Wang W C. Crystal structure of Helicobacter pylori oormamidaee AmiF reveals a cysteine-glutamate-lysine catalytic triad. Journal of Biological Chemistry, 2007, 282(16): 12220–12229
Ou X Y, Wu X L, Peng F, Zeng Y J, Li H X, Xu P, Chen G, Guo Z W, Yang J G, Zong M H, Lou W Y. Metabolic engineering of a robust Escherichia coli strain with a dual protection system. Biotechnology and Bioengineering, 2019, 116(12): 3333–3348
Brilon C, Beckmann W, Hellwig M, Knackmuss H J. Enrichment and isolation of naphthalenesulfonic acid-utilizing pseudomonads. Applied and Environmental Microbiology, 1981, 42(1): 39–43
Luther M, Soeder C J. 1-Naphthalenesulfonic acid and sulfate as sulfur sources for the green ALGA Scenedesmus obliquus. Water Research, 1991, 25(3): 299–307
Soeder C J, Hegewald E, Kneifel H. Green microalgae can use naphthalenesulfonic acids as sources of sulfur. Archives of Microbiology, 1987, 148(4): 260–263
Dopson M, Johnson D B. Biodiversity, metabolism and applications of acidophilic sulfur-metabolizing microorganisms. Environmental Microbiology, 2012, 14(10): 262–2631
Luther M, Soeder C J. Some naphthalenesulfonic acids as sulfur sources for the green microalga. Chemosphere, 1987, 16(7): 1565–1578
Cotter P D, Ross R P, Hill C. Bacteriocins—a viable alternative to antibiotics? Nature Reviews Microbiology, 2013, 11(2): 95–105
Qureshi A S, Zhang J, da Costa Sousa L, Bao J. Antibacterial peptide secreted by Pediococcus acidilactici enables efficient cellulosic open L -lactic acid fermentation. ACS Sustainable Chemistry & Engineering, 2017, 5(10): 9254–9262
Leroy F, Moreno M R F, De Vuyst L. Enterococcus faecium RZS C5, an interesting bacteriocin producer to be used as a co-culture in food fermentation. International Journal of Food Microbiology, 2003, 88(2–3): 235–240
Likhacheva N A, Samsonov V V, Samsonov V V, Sineoky S P. Genetic control of the resistance to phage C1 of Escherichia coli K-12. Journal of Bacteriology, 1996, 178(17): 5309–5315
Szczepankowska A K, Gorecki R K, Koakowski P, Bardowski J K. Lactic Acid Bacteria—R & D for Food, Health and Livestock Purposes. London: IntechOpen, 2013, 23–72
Sturino J M, Klaenhammer T R. Engineered bacteriophage-defence systems in bioprocessing. Nature Reviews Microbiology, 2006, 4(5): 395–404
Viscardi M, Capparelli R, Di Matteo R, Carminati D, Giraffa G, Iannelli D. Selection of bacteriophage-resistant mutants of Streptococcus thermophilus. Journal of Microbiological Methods, 2003, 55(1): 109–119
Mei Y J, Liu H. Selection of phage-resistant strains from Escherichia coli glyA genetic engineering bacteria. Agricultural Biotechnology, 2012, 1(2): 35–37
Fineran P C, Blower T R, Foulds I J, Humphreys D P, Lilley K S, Salmond G P. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106(3): 894–899
Reyes-Cortes R, Martinez-Penafiel E, Martinez-Perez F, de la Garza M, Kameyama L. A novel strategy to isolate cell-envelope mutants resistant to phage infection: bacteriophage mEp213 requires lipopolysaccharides in addition to FhuA to enter Escherichia coli K-12. Microbiology, 2012, 158(Pt 12): 3063–3071
Cowley L A, Low A S, Pickard D, Boinett C J, Dallman T J, Day M, Perry N, Gally D L, Parkhill J, Jenkins C, Cain A K. Transposon insertion sequencing elucidates novel gene involvement in susceptibility and resistance to phages T4 and T7 in Escherichia coli O157. mBio, 2018, 9(4): e00705–e00718
Tuncer Y, Akcelik M. A protein which masks galactose receptor mediated phage susceptibility in Lactococcus lactis subsp lactis MPL56. International Journal of Food Science & Technology, 2002, 37(2): 139–144
McGrath S, Fitzgerald G F, van Sinderen D. Identification and characterization of phage-resistance genes in temperate lactococcal bacteriophages. Molecular Microbiology, 2002, 43(2): 509–520
Dupuis M E, Villion M, Magadan A H, Moineau S. CRISPR-Cas and restriction-modification systems are compatible and increase phage resistance. Nature Communications, 2013, 4(1): 2087
Sturino J M, Klaenhammer T R. Expression of antisense RNA targeted against Streptococcus thermophilus bacteriophages. Applied and Environmental Microbiology, 2002, 68(2): 588–596
Burrus V, Bontemps C, Decaris B, Guedon G. Characterization of a novel type II restriction-modification system, Sth368I, encoded by the integrative element ICESt1 of Streptococcus thermophilus CNRZ368. Applied and Environmental Microbiology, 2001, 67(4): 1522–1528
Lucchini S, Sidoti J, Brussow H. Broad-range bacteriophage resistance in Streptococcus thermophilus by insertional mutagenesis. Virology, 2000, 275(2): 267–277
Sturino J M, Klaenhammer T R. Inhibition of bacteriophage replication in Streptococcus thermophilus by subunit poisoning of primase. Microbiology, 2007, 153(Pt 10): 3295–3302
Xue Y P, Shen Q, Zhou X T, Guo Q, Zheng Y G. Potential of the signal peptide derived from the PAS_chr3_0030 gene product for secretory expression of valuable enzymes in Pichia pastoris. Applied and Environmental Microbiology, 2021, 88(9): e0029622
Reyes-Cortes R, Arguijo-Hernandez E S, Carballo-Ontiveros M A, Martinez-Penafiel E, Kameyama L. Random transposon mutagenesis for cell-envelope resistant to phage infection. Methods in Molecular Biology, 2016, 1440: 71–83
Wang M S, Nitin N. Rapid detection of bacteriophages in starter culture using water-in-oil-in-water emulsion microdroplets. Applied Microbiology and Biotechnology, 2014, 98(19): 8347–8355
deMello A, Rane A, Holzner G, Stavrakis S. Ultra-high-throughput multi-parametric imaging flow cytometry. EPJ Web of Conferences, 2019, 215: 10001
Edgar R H, Cook J, Noel C, Minard A, Sajewski A, Fitzpatrick M, Fernandez R, Hempel J D, Kellum J A, Viator J A. Bacteriophage-mediated identification of bacteria using photoacoustic flow cytometry. Journal of Biomedical Optics, 2019, 24(11): 1–7
Viscardi M, Capparelli R, Iannelli D. Rapid selection of phage-resistant mutants in Streptococcus thermophilus by immunoselection and cell sorting. International Journal of Food Microbiology, 2003, 89(2–3): 223–231
Mutalik V K, Adler B A, Rishi H S, Piya D, Zhong C, Koskella B, Kutter E M, Calendar R, Novichkov P S, Price M N, Deutschbauer A M, Arkin A P. High-throughput mapping of the phage resistance landscape in E. coli. PLoS Biology, 2020, 18(10): e3000877
Maffei E, Shaidullina A, Burkolter M, Heyer Y, Estermann F, Druelle V, Sauer P, Willi L, Michaelis S, Hilbi H, Thaler D S, Harms A. Systematic exploration of Escherichia coli phage-host interactions with the BASEL phage collection. PLoS Biology, 2021, 19(11): e3001424
Barrangou R, Horvath P. CRISPR: new horizons in phage resistance and strain identification. Annual Review of Food Science and Technology, 2012, 3(1): 143–162
Chung D K, Chung S K, Batt C A. Antisense RNA directed against the major capsid protein of Lactococcus lactis subsp. cremoris bacteriophage 4-1 confers partial resistance to the host. Applied Microbiology and Biotechnology, 1992, 37(1): 79–83
Mahony J, McGrath S, Fitzgerald G F, van Sinderen D. Identification and characterization of lactococcal-prophage-carried superinfection exclusion genes. Applied and Environmental Microbiology, 2008, 74(20): 6206–6215
Ventura M, Canchaya C, Pridmore R D, Brussow H. The prophages of Lactobacillus johnsonii NCC 533: comparative genomics and transcription analysis. Virology, 2004, 320(2): 229–242
Sun X, Gohler A, Heller K J, Neve H. The ltp gene of temperate Streptococcus thermophilus phage TP-J34 confers superinfection exclusion to Streptococcus thermophilus and Lactococcus lactis. Virology, 2006, 350(1): 146–157
Garvey P, Hill C, Fitzgerald G F. The lactococcal plasmid pNP40 encodes a third bacteriophage resistance mechanism, one which affects phage DNA penetration. Applied and Environmental Microbiology, 1996, 62(2): 676–679
Kim J W, Dutta V, Elhanafi D, Lee S, Osborne J A, Kathariou S. A novel restriction-modification system is responsible for temperature-dependent phage resistance in Listeria monocytogenes ECII. Applied and Environmental Microbiology, 2012, 78(6): 1995–2004
Cong L, Zhang F. Genome engineering using CRISPR-Cas9 system. Methods in Molecular Biology, 2015, 1239: 197–217
Hsu P D, Lander E S, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell, 2014, 157(6): 1262–1278
Liu L, Zhao D, Ye L, Zhan T, Xiong B, Hu M, Bi C, Zhang X. A programmable CRISPR/Cas9-based phage defense system for Escherichia coli BL21(DE3). Microbial Cell Factories, 2020, 19(1): 136
Ofir G, Melamed S, Sberro H, Mukamel Z, Silverman S, Yaakov G, Doron S, Sorek R. DISARM is a widespread bacterial defence system with broad anti-phage activities. Nature Microbiology, 2018, 3(1): 90–98
Bernheim A, Sorek R. The pan-immune system of bacteria: antiviral defence as a community resource. Nature Reviews Microbiology, 2020, 18(2): 113–119
Chopin M C, Chopin A, Bidnenko E. Phage abortive infection in lactococci: variations on a theme. Current Opinion in Microbiology, 2005, 8(4): 473–479
Webster R E, Cashman J S. Abortive infection of Escherichia coli with the bacteriophage f1: cytoplasmic membrane proteins and the f1 DNA-gene 5 protein complex. Virology, 1973, 55(1): 20–38
Durmaz E, Klaenhammer T R. Abortive phage resistance mechanism AbiZ speeds the lysis clock to cause premature lysis of phage-infected Lactococcus lactis. Journal of Bacteriology, 2007, 189(4): 1417–1425
Xiong X, Wu G, Wei Y, Liu L, Zhang Y, Su R, Jiang X, Li M, Gao H, Tian X, Zhang Y, Hu L, Chen S, Tang Y, Jiang S, Huang R, Li Z, Wang Y, Deng Z, Wang J, Dedon P C, Chen S, Wang L. SspABCD-SspE is a phosphorothioation-sensing bacterial defence system with broad anti-phage activities. Nature Microbiology, 2020, 5(7): 917–928
Zou X, Xiao X, Mo Z, Ge Y, Jiang X, Huang R, Li M, Deng Z, Chen S, Wang L, Lee S Y. Systematic strategies for developing phage resistant Escherichia coli strains. Nature Communications, 2022, 13(1): 4491
Denamur E, Matic I. Evolution of mutation rates in bacteria. Molecular Microbiology, 2006, 60(4): 820–827
Umenhoffer K, Feher T, Baliko G, Ayaydin F, Posfai J, Blattner F R, Posfai G. Reduced evolvability of Escherichia coli MDS42, an IS-less cellular chassis for molecular and synthetic biology applications. Microbial Cell Factories, 2010, 9(1): 38
Vidal L, Pinsach J, Striedner G, Caminal G, Ferrer P. Development of an antibiotic-free plasmid selection system based on glycine auxotrophy for recombinant protein overproduction in Escherichia coli. Journal of Biotechnology, 2008, 134(1–2): 127–136
Zhang Y, Liu D, Chen Z. Production of C2–C4 diols from renewable bioresources: new metabolic pathways and metabolic engineering strategies. Biotechnology for Biofuels, 2017, 10(1): 299
Chen Z, Geng F, Zeng A P. Protein design and engineering of a de novo pathway for microbial production of 1,3-propanediol from glucose. Biotechnology Journal, 2015, 10(2): 284–289
Hagg P, de Pohl J W, Abdulkarim F, Isaksson L A. A host/plasmid system that is not dependent on antibiotics and antibiotic resistance genes for stable plasmid maintenance in Escherichia coli. Journal of Biotechnology, 2004, 111(1): 17–30
Porter R D, Black S, Pannuri S, Carlson A. Use of the Escherichia coli SSB gene to prevent bioreactor takeover by plasmidless cells. Biotechnology, 1990, 8(1): 47–51
Gerdes K, Poulsen L K, Thisted T, Nielsen A K, Martinussen J, Andreasen P H. The hok killer gene family in gram-negative bacteria. New Biology, 1990, 2(11): 946–956
Afif H, Allali N, Couturier M, Van-Melderen L. The ratio between CcdA and CcdB modulates the transcriptional repression of the ccd poison-antidote system. Molecular Microbiology, 2010, 41(1): 73–82
Terrinoni M, Nordqvist S L, Kallgard S, Holmgren J, Lebens M. A novel nonantibiotic, lgt -based selection system for stable maintenance of expression vectors in Escherichia coli and Vibrio cholerae. Applied and Environmental Microbiology, 2018, 84(4): e02143–e02117
Posfai G, Plunkett G III, Feher T, Frisch D, Keil G M, Umenhoffer K, Kolisnychenko V, Stahl B, Sharma S S, de Arruda M, Burland V, Harcum S W, Blattner F R. Emergent properties of reduced-genome Escherichia coli. Science, 2006, 312(5776): 1044–1046
Wyrzykowski J, Volkert M R. The Escherichia coli methyl-directed mismatch repair system repairs base pairs containing oxidative lesions. Journal of Bacteriology, 2003, 185(5): 1701–1704
Galan J C, Turrientes M C, Baquero M R, Rodriguez-Alcayna M, Martinez-Amado J, Martinez J L, Baquero F. Mutation rate is reduced by increased dosage of mutL gene in Escherichia coli K-12. FEMS Microbiology Letters, 2007, 275(2): 263–269
Csorgo B, Feher T, Timar E, Blattner F R, Posfai G. Low-mutation-rate, reduced-genome Escherichia coli: an improved host for faithful maintenance of engineered genetic constructs. Microbial Cell Factories, 2012, 11(1): 11
Michener J K, Thodey K, Liang J C, Smolke C D. Applications of genetically-encoded biosensors for the construction and control of biosynthetic pathways. Metabolic Engineering, 2012, 14(3): 212–222
Snoek T, Romero-Suarez D, Zhang J, Ambri F, Skjoedt M L, Sudarsan S, Jensen M K, Keasling J D. An orthogonal and pH-tunable sensor-selector for muconic acid biosynthesis in yeast. ACS Synthetic Biology, 2018, 7(4): 995–1003
Crook N, Abatemarco J, Sun J, Wagner J M, Schmitz A, Alper H S. In vivo continuous evolution of genes and pathways in yeast. Nature Communications, 2016, 7(1): 13051
Zhang X, Jantama K, Moore J C, Jarboe L R, Shanmugam K T, Ingram L O. Metabolic evolution of energy-conserving pathways for succinate production in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America, 2009, 106(48): 20180–20185
Hauf J, Zimmermann F K, Muller S. Simultaneous genomic overexpression of seven glycolytic enzymes in the yeast Saccharomyces cerevisiae. Enzyme and Microbial Technology, 2000, 26(9–10): 688–698
Yamamoto S, Gunji W, Suzuki H, Toda H, Suda M, Jojima T, Inui M, Yukawa H. Overexpression of genes encoding glycolytic enzymes in Corynebacterium glutamicum enhances glucose metabolism and alanine production under oxygen deprivation conditions. Applied and Environmental Microbiology, 2012, 78(12): 4447–4457
Ma W, Wang J, Li Y, Hu X, Shi F, Wang X. Enhancing pentose phosphate pathway in Corynebacterium glutamicum to improve L-isoleucine production. Biotechnology and Applied Biochemistry, 2016, 63(6): 877–885
Irani N, Beccaria A J, Wagner R. Expression of recombinant cytoplasmic yeast pyruvate carboxylase for the improvement of the production of human erythropoietin by recombinant BHK-21 cells. Journal of Biotechnology, 2002, 93(3): 269–282
Wang Z, Chen T, Ma X, Shen Z, Zhao X. Enhancement of riboflavin production with Bacillus subtilis by expression and site-directed mutagenesis of zwf and gnd gene from Corynebacterium glutamicum. Bioresource Technology, 2011, 102(4): 3934–3940
Koebmann B J, Westerhoff H V, Snoep J L, Nilsson D, Jensen P R. The glycolytic flux in Escherichia coli is controlled by the demand for ATP. Journal of Bacteriology, 2002, 184(14): 3909–3916
Causey T B, Shanmugam K T, Yomano L P, Ingram L O. Engineering Escherichia coli for efficient conversion of glucose to pyruvate. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(8): 2235–2240
Causey T B, Zhou S, Shanmugam K T, Ingram L O. Engineering the metabolism of Escherichia coli W3110 for the conversion of sugar to redox-neutral and oxidized products: homoacetate production. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(3): 825–832
Wang J, Niyompanich S, Tai Y S, Wang J, Bai W, Mahida P, Gao T, Zhang K. Engineering of a highly efficient Escherichia coli strain for mevalonate fermentation through chromosomal integration. Applied and Environmental Microbiology, 2016, 82(24): 7176–7184
Kou M, Cui Z, Fu J, Dai W, Wang Z, Chen T. Metabolic engineering of Corynebacterium glutamicum for efficient production of optically pure (2R, 3R)-2,3-butanediol. Microbial Cell Factories, 2022, 21(1): 150
Luo Z, Zeng W, Du G, Chen J, Zhou J. Enhanced pyruvate production in Candida glabrata by engineering ATP futile cycle system. ACS Synthetic Biology, 2019, 8(4): 787–795
Fuentes L G, Lara A R, Martinez L M, Ramirez O T, Martinez A, Bolivar F, Gosset G. Modification of glucose import capacity in Escherichia coli: physiologic consequences and utility for improving DNA vaccine production. Microbial Cell Factories, 2013, 12(1): 42
Ikeda M. Sugar transport systems in Corynebacterium glutamicum: features and applications to strain development. Applied Microbiology and Biotechnology, 2012, 96(5): 1191–1200
Zhou Z, Wang C, Xu H, Chen Z, Cai H. Increasing succinic acid production using the PTS-independent glucose transport system in a Corynebacterium glutamicum PTS-defective mutant. Journal of Industrial Microbiology & Biotechnology, 2015, 42(7): 1073–1082
Hernandez-Montalvo V, Martinez A, Hernandez-Chavez G, Bolivar F, Valle F, Gosset G. Expression of galP and glk in a Escherichia coli PTS mutant restores glucose transport and increases glycolytic flux to fermentation products. Biotechnology and Bioengineering, 2003, 83(6): 687–694
Lu J, Tang J, Liu Y, Zhu X, Zhang T, Zhang X. Combinatorial modulation of galP nnd glk gene expression for improved alternative glucose utilization. Applied Microbiology and Biotechnology, 2012, 93(6): 2455–2462
Hao Y, Ma Q, Liu X, Fan X, Men J, Wu H, Jiang S, Tian D, Xiong B, Xie X. High-yield production of L-valine in engineered Escherichia coli by a novel two-stage fermentation. Metabolic Engineering, 2020, 62: 198–206
Michalowski A, Siemann-Herzberg M, Takors R. Escherichia coli HGT: engineered for high glucose throughput even under slowly growing or resting conditions. Metabolic Engineering, 2017, 40: 93–103
Zhang X, Lai L, Xu G, Zhang X, Shi J, Koffas M A G, Xu Z. Rewiring the central metabolic pathway for high-yield L-serine production in Corynebacterium glutamicum by using glucose. Biotechnology Journal, 2019, 14(6): e1800497
Zhan Y, Shi J, Xiao Y, Zhou F, Wang H, Xu H, Li Z, Yang S, Cai D, Chen S. Multilevel metabolic engineering of Bacillus licheniformis for de novo biosynthesis of 2-phenylethanol. Metabolic Engineering, 2022, 70: 43–54
Gu Y, Deng J, Liu Y, Li J, Shin H D, Du G, Chen J, Liu L. Rewiring the glucose transportation and central metabolic pathways for overproduction of N-acetylglucosamine in Bacillus subtilis. Biotechnology Journal, 2017, 12(10): 170020
Long C P, Gonzalez J E, Feist A M, Palsson B O, Antoniewicz M R. Fast growth phenotype of E. coli K-12 from adaptive laboratory evolution does not require intracellular flux rewiring. Metabolic Engineering, 2017, 44: 100–107
Dragosits M, Mattanovich D. Adaptive laboratory evolution—principles and applications for biotechnology. Microbial Cell Factories, 2013, 12(1): 64
Portnoy V A, Bezdan D, Zengler K. Adaptive laboratory evolution—harnessing the power of biology for metabolic engineering. Current Opinion in Biotechnology, 2011, 22(4): 590–594
Shen Y, Chen X, Peng B, Chen L, Hou J, Bao X. An efficient xylose-fermenting recombinant Saccharomyces cerevisiae strain obtained through adaptive evolution and its global transcription profile. Applied Microbiology and Biotechnology, 2012, 96(4): 1079–1091
Guimaraes P M, Francois J, Parrou J L, Teixeira J A, Domingues L. Adaptive evolution of a lactose-consuming Saccharomyces cerevisiae recombinant. Applied and Environmental Microbiology, 2008, 74(6): 1748–1756
Radek A, Tenhaef N, Muller M F, Brusseler C, Wiechert W, Marienhagen J, Polen T, Noack S. Miniaturized and automated adaptive laboratory evolution: evolving Corynebacterium glutamicum towards an improved D-xylose utilization. Bioresource Technology, 2017, 245(Pt B): 1377–1385
McCloskey D, Xu S, Sandberg T E, Brunk E, Hefner Y, Szubin R, Feist A M, Palsson B O. Adaptive laboratory evolution resolves energy depletion to maintain high aromatic metabolite phenotypes in Escherichia coli strains lacking the Phosphotransferase System. Metabolic Engineering, 2018, 48: 233–242
Reyes L H, Gomez J M, Kao K C. Improving carotenoids production in yeast via adaptive laboratory evolution. Metabolic Engineering, 2014, 21(1): 26–33
Mahr R, Gatgens C, Gatgens J, Polen T, Kalinowski J, Frunzke J. Biosensor-driven adaptive laboratory evolution of L-valine production in Corynebacterium glutamicum. Metabolic Engineering, 2015, 32: 184–194
Niu F X, He X, Wu Y Q, Liu J Z. Enhancing production of pinene in Escherichia coli by using a combination of tolerance, evolution, and modular co-culture engineering. Frontiers in Microbiology, 2018, 9: 1623
Tuyishime P, Wang Y, Fan L, Zhang Q, Li Q, Zheng P, Sun J, Ma Y. Engineering Corynebacterium glutamicum for methanol-dependent growth and glutamate production. Metabolic Engineering, 2018, 49: 220–231
Minliang C, Chengwei M, Lin C, Zeng A P. Integrated laboratory evolution and rational engineering of GalP/Glk-dependent Escherichia coli for higher yield and productivity of L-tryptophan biosynthesis. Metabolic Engineering Communications, 2021, 12: e00167
Cheng J S, Qiao B, Yuan Y J. Comparative proteome analysis of robust Saccharomyces cerevisiae insights into industrial continuous and batch fermentation. Applied Microbiology and Biotechnology, 2008, 81(2): 327–338
Nicolaou S A, Gaida S M, Papoutsakis E T. A comparative view of metabolite and substrate stress and tolerance in microbial bioprocessing: from biofuels and chemicals, to biocatalysis and bioremediation. Metabolic Engineering, 2010, 12(4): 307–331
Jia K, Zhang Y, Yin L. Systematic engineering of microorganisms to improve alcohol tolerance. Engineering in Life Sciences, 2010, 10(5): 422–429
Calamita G, Bishai W R, Preston G M, Guggino W B, Agre P. Molecular cloning and characterization of AqpZ, a water channel from Escherichia coli. Journal of Biological Chemistry, 1995, 270(49): 29063–29066
Laimins L A, Rhoads D B, Epstein W. Osmotic control of kdp operon expression in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America, 1981, 78(1): 464–468
Sevin D C, Sauer U. Ubiquinone accumulation improves osmotic-stress tolerance in Escherichia coli. Nature Chemical Biology, 2014, 10(4): 266–272
Ma R, Zhang Y, Hong H, Lu W, Lin M, Chen M, Zhang W. Improved osmotic tolerance and ethanol production of ethanologenic Escherichia coli by IrrE, a global regulator of radiation-resistance of Deinococcus radiodurans. Current Microbiology, 2011, 62(2): 659–664
Pan J, Wang J, Zhou Z, Yan Y, Zhang W, Lu W, Ping S, Dai Q, Yuan M, Feng B, Hou X, Zhang Y, Ruiqiang M, Liu T, Feng L, Wang L, Chen M, Lin M. IrrE, a global regulator of extreme radiation resistance in Deinococcus radiodurans, enhances salt tolerance in Escherichia coli and Brassica napus. PLoS One, 2009, 4(2): e4422
Stasic A J, Lee Wong A C, Kaspar C W. Osmotic and desiccation tolerance in Escherichia coli O157:H7 requires rpoS (sigma(38)). Current Microbiology, 2012, 65(6): 660–665
Grothe S, Krogsrud R L, McClellan D J, Milner J L, Wood J M. Proline transport and osmotic stress response in Escherichia coli K-12. Journal of Bacteriology, 1986, 166(1): 253–259
JrM T R, Courtenay E S, Cayley D S, Guttman H J. Responses of E. coli to osmotic stress: large changes in amounts of cytoplasmic solutes and water. Trends in Biochemical Sciences, 1998, 23(4): 143–148
Weymarn N V, Nyyssola A, Reinikainen T, Leisola M, Ojamo H. Improved osmotolerance of recombinant Escherichia coli by de novo glycine betaine biosynthesis. Applied Microbiology and Biotechnology, 2000, 55(2): 214–218
Aranda A, Querol A, del Olmo M. Correlation between acetaldehyde and ethanol resistance and expression of HSP genes in yeast strains isolated during the biological aging of sherry wines. Archives of Microbiology, 2002, 177(4): 304–312
Jiang C, Xu J, Zhang H, Zhang X, Shi J, Li M, Ming F. A cytosolic class I small heat shock protein, RcHSP17.8, of Rosa chinensis confers resistance to a variety of stresses to Escherichia coli, yeast and Arabidopsis thaliana. Plant, Cell & Environment, 2009, 32(8): 1046–1059
Seydlova G, Halada P, Fiser R, Toman O, Ulrych A, Svobodova J. DnaK and GroEL chaperones are recruited to the Bacillus subtilis membrane after short-term ethanol stress. Journal of Applied Microbiology, 2012, 112(4): 765–774
Zingaro K A, Terry Papoutsakis E. GroESL overexpression imparts Escherichia coli tolerance to i-, n-, and 2-butanol, 1,2,4-butanetriol and ethanol with complex and unpredictable patterns. Metabolic Engineering, 2013, 15: 196–205
Sridhar M, Sree N K, Rao L V. Effect of UV radiation on thermotolerance, ethanol tolerance and osmotolerance of Saccharomyces cerevisiae VS1 and VS3 strains. Bioresource Technology, 2002, 83(3): 199–202
Yu L, Pei X, Lei T, Wang Y, Feng Y. Genome shuffling enhanced L -lactic acid production by improving glucose tolerance of Lactobacillus rhamnosus. Journal of Biotechnology, 2008, 134(1–2): 154–159
Zheng D Q, Wu X C, Tao X L, Wang P M, Li P, Chi X Q, Li Y D, Yan Q F, Zhao Y H. Screening and construction of Saccharomyces cerevisiae strains with improved multi-tolerance and bioethanol fermentation performance. Bioresource Technology, 2011, 102(3): 3020–3027
Xiao M, Zhu X, Fan F, Xu H, Tang J, Qin Y, Ma Y, Zhang X. Osmotolerance in Escherichia coli is improved by activation of copper efflux genes or supplementation with sulfur-containing amino acids. Applied and Environmental Microbiology, 2017, 83(7): e03050–e03016
Zhu X, Tan Z, Xu H, Chen J, Tang J, Zhang X. Metabolic evolution of two reducing equivalent-conserving pathways for high-yield succinate production in Escherichia coli. Metabolic Engineering, 2014, 24: 87–96
Jensen S I, Lennen R M, Herrgard M J, Nielsen A T. Seven gene deletions in seven days: fast generation of Escherichia coli strains tolerant to acetate and osmotic stress. Scientific Reports, 2015, 5(1): 17874
Lennen R M, Herrgard M J. Combinatorial strategies for improving multiple-stress resistance in industrially relevant Escherichia coli strains. Applied and Environmental Microbiology, 2014, 80(19): 6223–6242
Yang L B, Dai X M, Zheng Z Y, Zhu L, Zhan X B, Lin C C. Proteomic analysis of erythritol-producing Yarrowia lipolytica from glycerol in response to osmotic pressure. Journal of Microbiology and Biotechnology, 2015, 25(7): 1056–1069
Chen X, Yin J, Ye J, Zhang H, Che X, Ma Y, Li M, Wu L P, Chen G Q. Engineering Halomonas bluephagenesis TD01 for non-sterile production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate). Bioresource Technology, 2017, 244(Pt 1): 534–541
Hoffart E, Grenz S, Lange J, Nitschel R, Müller F, Schwentner A, Feith A, Lenfers-Lücker M, Takors R, Blombach B. High substrate uptake rates empower Vibrio natriegens as production host for industrial biotechnology. Applied and Environmental Microbiology, 2017, 83(22): e01614–e01617
Weinstock M T, Hesek E D, Wilson C M, Gibson D G. Vibrio natriegens as a fast-growing host for molecular biology. Nature Methods, 2016, 13(10): 849–851
Saha B C, Kennedy G J. Efficient itaconic acid production by Aspergillus terreus: overcoming the strong inhibitory effect of manganese. Biotechnology Progress, 2020, 36(2): e2939
Tevz G, Bencina M, Legisa M. Enhancing itaconic acid production by Aspergillus terreus. Applied Microbiology and Biotechnology, 2010, 87(5): 1657–1664
Voulgaris I, O’Donnell A, Harvey L M, McNeil B. Inactivating alternative NADH dehydrogenases: enhancing fungal bioprocesses by improving growth and biomass yield? Scientific Reports, 2012, 2(1): 322
Zhang J, Wu N, Ou W, Li Y, Liang Y, Peng C, Li Y, Xu Q, Tong Y. Peptide supplementation relieves stress and enhances glycolytic flux in filamentous fungi during organic acid bioproduction. Biotechnology and Bioengineering, 2022, 119(9): 2471–2481
Tschirhart T, Shukla V, Kelly E E, Schultzhaus Z, NewRingeisen E, Erickson J S, Wang Z, Garcia W, Curl E, Egbert R G, Yeung E, Vora G J. Synthetic biology tools for the fast-growing marine bacterium Vibrio natriegens. ACS Synthetic Biology, 2019, 8(9): 2069–2079
Gao F, Hao Z, Sun X, Qin L, Zhao T, Liu W, Luo H, Yao B, Su X. A versatile system for fast screening and isolation of Trichoderma reesei cellulase hyperproducers based on DsRed and fluorescence-assisted cell sorting. Biotechnology for Biofuels, 2018, 11(1): 261
Acknowledgements
This work was supported by the National Key R&D Program of China (Grant No. 2021YFC2100900), the National Natural Science Foundation of China (Grant Nos. 21938004, 22078172, and 21878172), and DongGuan Innovative Research Team Program (Grant No. 201536000100033).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Dong, Y., Zhang, Y., Liu, D. et al. Strain and process engineering toward continuous industrial fermentation. Front. Chem. Sci. Eng. 17, 1336–1353 (2023). https://doi.org/10.1007/s11705-022-2284-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11705-022-2284-6