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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

邮发代号 80-969

2019 Impact Factor: 3.552

Frontiers of Chemical Science and Engineering  2023, Vol. 17 Issue (10): 1336-1353   https://doi.org/10.1007/s11705-022-2284-6
  本期目录
Strain and process engineering toward continuous industrial fermentation
Yufei Dong1, Ye Zhang1, Dehua Liu1,2,3, Zhen Chen1,2,3()
1. Key Laboratory of Industrial Biocatalysis (Ministry of Education), Department of Chemical Engineering, Tsinghua University, Beijing 100084, China
2. Tsinghua Innovation Center in Dongguan, Dongguan 523808, China
3. Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China
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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.

Key wordscontinuous fermentation    productivity    contamination    strain degeneration    metabolic engineering
收稿日期: 2022-09-28      出版日期: 2023-10-07
Corresponding Author(s): Zhen Chen   
 引用本文:   
. [J]. Frontiers of Chemical Science and Engineering, 2023, 17(10): 1336-1353.
Yufei Dong, Ye Zhang, Dehua Liu, Zhen Chen. Strain and process engineering toward continuous industrial fermentation. Front. Chem. Sci. Eng., 2023, 17(10): 1336-1353.
 链接本文:  
https://academic.hep.com.cn/fcse/CN/10.1007/s11705-022-2284-6
https://academic.hep.com.cn/fcse/CN/Y2023/V17/I10/1336
Product Strain Culture time Ref.
PHAa) Halomonas campaniensis LS21 65 days [11]
Ethanol Saccharomyces cerevisiae 141 days [12]
Beer Immobilized yeast cell 35 days [13]
Ethanol and yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe (SPSC 01) 40 days [14]
Biohydrogen Seed sludge from a local municipal wastewater treatment plant 200 days [15]
Lactic acid Lactobacillus rhamnosus 350 h [16]
L-lysine Corynebacterium glutamicum B-6 500 h [17]
Succinic acid Actinobacillus succinogenes 18 days [18]
ABEb) Clostridium acetobutylicum 300 h [19]
1,3-Propanediol Clostridium butyricum 16 days [20]
Butanol Immobilized Clostridium acetobutylicum 1000 h [21]
Tab.1  
Product Strain Fermentation type Titer Yield Productivity Ref.
Ethanol Saccharomyces cerevisiae Batch fermentation ~114.0 g·L–1 97% of the theoretical 16.2 g·L–1·h–1 [8]
Saccharomyces cerevisiae Continuous fermentation 60.5 g·L–1 95% of the theoretical 32.0 g·L–1·h–1 [8]
Lactic acid Lactobacillus casei Fed-batch 210 g·L–1 90.3% 2.14 g·L–1·h–1 [9]
Lactobacillus rhamnosus Continuous fermentation Not reported 68.8% 8.18 g·L–1·h–1 [16]
L-lysine Corynebacterium glutamicum Fed-batch fermentation 100 g·L–1 Not reported ~2.1 g·L–1·h–1 [17]
Corynebacterium glutamicum Continuous fermentation 105 g·L–1 0.385 g·g–1 5.6 g·L–1·h–1 [17]
1,3-Propanediol Clostridium butyricum Fed-batch fermentation 67.9 g·L–1 0.55 g·g–1 0.78 g·L–1·h–1 [20]
Clostridium butyricum Continuous fermentation 30.1 g·L–1 0.52 g·g–1 1.87 g·L–1·h–1 [20]
Butanol (ABE) Clostridium acetobutylicum Batch fermentation < 11 g·L–1 0.175 g·g–1 0.17 g·L–1·h–1 [19]
Clostridium acetobutylicum Continuous fermentation 5.1 g·L–1 0.42 g·g–1 4.6 g·L–1·h–1 [21]
Tab.2  
Fig.1  
Fig.2  
Species Biophage Approach description Ref.
E. coli DH5α Phage ФTB16–25 A plasmid-encoded Abi (abortive infection) system, ToxIN, promotes cell death, and limits phage replication [60]
E. coli GlyA Phage ESP1 Phage-induced screen and UV-coupling phage-induced screen [59]
E. coli K-12 Phage mEp213, phage λ Phage-induced screen combining transposon mutagenesis [61]
E. coli O157 Phage T4, phage T7 Phage-induced screen combining transposon mutagenesis [62]
L. lactis Phage Фmpl51, Фmpl86, Фmpl961, Фmpl1083 A plasmid-encoded protein to inhibit phage adsorption by masking phage receptor [63]
L. lactis Phage Tuc2009 A phage-encoded superinfection exclusion (Sie) to block phage DNA injection [64]
S. thermophilus Phage 2972 Combine clustered regularly interspaced short palindromic regions (CRISPR)-CRISPR-associated (Cas) and restriction−modification (R−M) systems [65]
S. thermophilus Phage к1, к3, к4, к5 Expression of Antisense RNA complementary to putative helicase gene to interfere phage transcription [66]
S. thermophilus CNRZ368 Phage ФST51 A novel type II R−M system, Sth368I, to cleave invade phage genome [67]
S. thermophilus Sfi1 Phage Sfi19 and heterologous phages Phage-induced screen combining thermolabile insertional vector [68]
S. thermophilus NCK1125 Phage к3 Expression of a mutant primase in trans to inhibit phage replication [69]
Tab.3  
Fig.3  
Fig.4  
Fig.5  
Fig.6  
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