Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2020, Vol. 40 Issue (6): 93-99    DOI: 10.13523/j.cb.2002046
综述     
工业微生物发酵过程中pH调控研究进展 *
高小朋1,**(),何猛超1,许可2,3,**(),李春1,2,3
1 延安大学生命科学学院 延安 716000
2 清华大学化学工程系 北京 100084
3 北京理工大学化学与化工学院 合成生物系统研究所 北京 100081
Research Progress on pH Regulation in the Process of Industrial Microbial Fermentation
GAO Xiao-peng1,**(),HE Meng-chao1,XU Ke2,3,**(),LI Chun1,2,3
1 School of Life Science, Yan’an University, Yan’an 716000, China
2 Department of Chemical Engineering, Tsinghua University, Beijing 100084, China
3 Department of Biochemical Engineering, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China
 全文: PDF(648 KB)   HTML
摘要:

pH是影响微生物生长的重要因素。工业发酵过程中,pH调控波动产生酸/碱胁迫,进而影响到微生物细胞的生长及目标产物的积累。阐述了工业微生物在发酵体系pH波动时所发生的生理变化,总结了目前工业发酵中pH调控的主要策略及各自的优缺点,并指出了未来pH调控的发展方向,以期为发酵工业pH调控提供新的思路。

关键词: 工业微生物酸碱胁迫pH调控策略    
Abstract:

PH is an important factor affecting the growth of microorganisms. In the process of industrial fermentation, the fluctuation of pH regulation could lead to acid / alkali stresses, which affects the growth of microbial cells and the accumulation of target products. In this review, the physiological changes of industrial microorganisms in the pH fluctuation of fermentation system were described, and the main strategies of pH regulation in industrial fermentation and the comparison of them were summarized. Furthermore, the development direction of pH regulation in the future was pointed out, as it can provide new ideas for pH regulation in fermentation industry.

Key words: Industrial microorganism    Acid/alkali stress    pH regulation
收稿日期: 2020-02-27 出版日期: 2020-06-23
ZTFLH:  Q819  
基金资助: * 国家自然科学基金(21868038)
通讯作者: 高小朋,许可     E-mail: gaoxiaopengyd@163.com;xuke528@tsinghua.edu.cn
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  
高小朋
何猛超
许可
李春

引用本文:

高小朋,何猛超,许可,李春. 工业微生物发酵过程中pH调控研究进展 *[J]. 中国生物工程杂志, 2020, 40(6): 93-99.

GAO Xiao-peng,HE Meng-chao,XU Ke,LI Chun. Research Progress on pH Regulation in the Process of Industrial Microbial Fermentation. China Biotechnology, 2020, 40(6): 93-99.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2002046        https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I6/93

微生物种类 最低pH 最适pH 最高pH
Escherichia coli 4.3 6.5~7.5 9.5[16]
Bacillus subtilis 4.5 6.5~7.5 8.5[17]
Staphylococcus aureus 4.2 7.0~7.5 9.3[18]
Aspergillus niger 1.5 5.0~6.0 9.0[19]
Lactobacillus acidophilus 4.0 5.8~6.6 6.8[20]
Corynebacterium glutamate 5.5 7.0~8.5 10.0[21]
Saccharomyces cerevisiae 4.0~4.5 7.5[22]
表1  部分常见微生物的最适pH
图1  微生物胞内pH的动态平衡机制
图2  微生物胞内质子泵的作用机制[35]
[1] Liu Z, Wang K, Chen Y , et al. Third-generation biorefineries as the means to produce fuels and chemicals from CO2. Nature Catalysis, 2020,3(3):274-88.
[2] 谭天伟, 苏海佳, 陈必强 , 等. 绿色生物制造. 北京化工大学学报, 2018,45(5):107-18
Tan T W, Su H J, Chen B Q , et al. Green bio-manufacturing. Journal of Beijing University of Chemical Technology, 2018,45(5):107-18.
[3] Xu K, Lee Y S, Li J , et al. Resistance mechanisms and reprogramming of microorganisms for efficient biorefinery under multiple environmental stresses. Synthetic and Systems Biotechnology, 2019,4(2):92-98.
pmid: 30899819
[4] Xu K, Lv B, Huo Y X , et al. Toward the lowest energy consumption and emission in biofuel production: combination of ideal reactors and robust hosts. Current Opinion in Biotechnology, 2017. 50:19-24.
doi: 10.1016/j.copbio.2017.08.011 pmid: 28892666
[5] Krulwich T A, Sachs G, Padan E , et al. Molecular aspects of bacterial pH sensing and homeostasis. Nature Reviews Microbiology, 2011. 9(5):330-343.
[6] Ghaffar T, Irshad M, Anwar Z , et al. Recent trends in lactic acid biotechnology: a brief review on production to purification. Journal of Radiation Research and Applied Sciences, 2014. 7(2):222-229.
[7] Jiang L, Cui H, Zhu L , et al. Enhanced propionic acid production from whey lactose with immobilized Propionibacterium acidipropionici and the role of trehalose synthesis in acid tolerance. Green Chemistry, 2015,17:250-259.
[8] Seme H, Gjuracic K, Kos B , et al. Acid resistance and response to pH-induced stress in two Lactobacillus plantarum strains with probiotic potential. Beneficial Microbes, 2014,6(3):369-379.
[9] Krulwich T A, Sachs G, Padan E . Molecular aspects of bacterial pH sensing and homeostasis. Nat Rev Microbiol, 2011,9(5):330-343.
pmid: 21464825
[10] 曹艳, 丁健, 段作营 , 等. 在线推定和控制葡萄糖浓度改善谷氨酸发酵性能. 微生物学通报, 2009,10(36):1619-1624.
Cao Y, Ding J, Cao Z Y , et al. On-line glucose concentration prediction and control for improving glutamate fermentation performance. Microbiology, 2009,10(36):1619-1624.
[11] Balat M , Production of bioethanol from lignocellulosic materials via the biochemical pathway: a review. Energy Conversion and Management, 2011,52(2):858-875.
[12] 冯年群 . 酿酒酵母高密度发酵生产谷胱甘肽的研究. 杭州:浙江大学, 2013.
Feng N Q . The production of glutathione through high cell density culture with Saccharomyces cerevisiae. Hangzhou: Zhejiang University, 2013.
[13] Selale O G, Tari C, Unluturk S . Effect of various process parameters on morphology, rheology, and polygalacturonase production by Aspergillus sojae in a batch bioreactor. Biotechnology Progress, 2007,23(4):836-845.
doi: 10.1021/bp070079c pmid: 17585778
[14] 赵心清, 张明明, 徐桂红 , 等. 酿酒酵母乙酸耐性分子机制的功能基因组进展. 生物工程学报, 2014,30(3):368-380.
Zhao X Q, Zhang M M, Xu G H , et al. Advances in functional genomics studies underlying acetic acid tolerance of Saccharomyces cerevisiae. Chinese Journal of Biotechnology, 2014,30(3):368-380.
[15] Andersson C, Petrova E, Berglund K , et al. Maintaining high anaerobic succinic acid productivity by product removal. Bioprocess & Biosystems Engineering, 2010. 33(6):711-718.
pmid: 19921276
[16] Philip P, Meier K, Kern D , et al. Systematic evaluation of characteristics of the membrane-based fed-batch shake flask. Microbial Cell Factories, 2018,16(1):122.
[17] 吴青录, 秦秀丽 , 枯草芽孢杆菌液体培养条件的研究. 吉林农业, 2012(4):65-65.
Wu Q L, Qin X L , Study on the liquid culture conditions of Bacillus subtilis. Jilin Agriculture, 2012(4):65-65.
[18] 张哲, 李新圃, 杨峰 , 等. 金黄色葡萄球菌培养基的筛选及发酵条件的优化研究. 微生物学杂志, 2018,38(3):42-47.
Zhang Z, Li X P, Yang F , et al. Culture medium screening and fermentation conditions optimization for Staphylococcus aureus. Journal of Microbiology, 2018,38(3):42-47.
[19] 邢亚梅, 陈勇, 应汉杰 . 黑曲霉(Aspergillus niger)发酵生产木聚糖酶的pH调控策略. 生物加工过程, 2015,13(1):23-27.
Xing Y M, Chen Y, Ying H J . Two-stage pH control strategy for xylanase production by Aspergillus niger D08. Chinese Journal of Bioprocess Engineering, 2015,13(1):23-27.
[20] 王天云, 陈振风, 王福源 . 嗜酸乳杆菌在不同pH条件下生长和存活情况的研究. 工业微生物, 2000,30(3):12-15.
Wang T Y, Chen Z F, Wang F Y . Growth and survival of Lactobacillus acidophilus at different pH. Industrial Microbiology, 2000,30(3):12-15.
[21] Liu Y, Yang X, Yin Y , et al. Mycothiol protects Corynebacterium glutamicum against acid stress via maintaining intracellular pH homeostasis, scavenging ROS, and S-mycothiolating MetE. Journal of General and Applied Microbiology, 2016,62(3):144-153.
doi: 10.2323/jgam.2016.02.001 pmid: 27250661
[22] Callari R, Fischer D, Heider H , et al. Biosynthesis of angelyl-CoA in Saccharomyces cerevisiae. Microbial Cell Factories, 2018,17(1):72.
pmid: 29753326
[23] Sohlenkamp C . Membrane homeostasis in bacteria upon pH challenge. Biogenesis of Fatty Acids, Lipids and Membranes, 2019: 787-799.
[24] Qi Y, Liu H, Chen X , et al. Engineering microbial membranes to increase stress tolerance of industrial strains. Metabolic Engineering, 2019,53:24-34.
[25] Siliakus M F, John V D O, Kengen, Serve W M . Adaptations of archaeal and bacterial membranes to variations in temperature, pH and pressure. Extremophiles, 2017,21(4):651-670.
[26] Yan D, Lin X, Qi Y , et al. Crz1p regulates pH homeostasis in Candida glabrata by altering membrane lipid composition. Applied Environmental Microbiology, 2016,82(23):6920-6929.
[27] Kaiser J C, Sen S, Sinha A , et al. The role of two branched-chain amino acid transporters in Staphylococcus aureus growth, membrane fatty acid composition, and virulence. Molecular Microbiology, 2016,102(5):850-864.
pmid: 27589208
[28] Foster J W . Escherichia coli acid resistance: tales of an amateur acidophile. Nature Reviews Microbiology, 2004,2(11):898-907.
[29] Guan N, Liu L, Shin H D , et al. Systems-level understanding of how Propioni bacterium acid ipropionici respond to propionic acid stress at the microenvironment levels: mechanism and application. Journal of Biotechnology, 2013,167(1):56-63.
[30] Kobayashi H, Suzuki T, Unemoto T . Streptococcal cytoplasmic pH is regulated by changes in amount and activity of a proton-translocating atpase. Journal of Biological Chemistry, 1986,261:627-63.
[31] Krulwich TA, Sachs G, Padan E . Molecular aspects of bacterial pH sensing and homeostasis. Nat Rev Microbiol, 2011,9(5):330-343.
doi: 10.1038/nrmicro2549 pmid: 21464825
[32] Follmann M, Becker M, Ochrombel I , et al. Potassium transport in Corynebacterium glutamicum is facilitated by the putative channel protein CglK, which is essential for pH homeostasis and growth at acidic pH. Journal of Bacteriology, 2009,191(9):2944-2952.
[33] Xu N, Lv H, Wei L , et al. Impaired oxidative stress and sulfur assimilation contribute to acid tolerance of Corynebacterium glutamicum. Applied Microbiology and Biotechnology, 2019,103(4):1877-1891.
[34] Sun Y . F1F0-ATPase functions under markedly acidic conditions in bacteria, Regulation of Ca2+-ATPases, V-ATPases and F-ATPases, 2016,14:459-468.
[35] 吕春微, 李霜, 徐晴 . 工业微生物的酸胁迫响应及其抵御策略. 中国生物工程杂志, 2014,34(3):132-137.
Lv C W, Li S, Xu Q , Response and resistance of acid stress in industry microbiology. China Biotechnology, 2014,34(3):132-137.
[36] Guan N, Liu L . Microbial response to acid stress: mechanisms and applications. Applied Microbiology and Biotechnology, 2020,104(1):51-65.
[37] 田丰伟, 尹义敏, 翟齐啸 , 等. 细胞膜ATPase活性和膜脂肪酸组成对植物乳杆菌耐酸性的影响. 中国食品学报, 2016,16(12):17-22.
Tian F W, Yi Y M, Zhai Q X , et al. Effect of membrane’s ATPase activity and lipid profile on the acid tolerance of Lactobacillus plantarum. Journal of Chinese Instistute of Food Science and Technology, 2016,016(012):17-22.
[38] Peter L, Angela T, Daniela D B . Coping with low pH: molecular strategies in neutralophilic bacteria. FEMS Microbiology Reviews, 2014,38(6):1091-1125.
pmid: 24898062
[39] Luo Y, Helmann J D . Analysis of the role of Bacillus subtilis, σ M in β-lactam resistance reveals an essential role for c‐di‐AMP in peptidoglycan homeostasis. Molecular Microbiology, 2012,83(3):623-639.
[40] Calhoun L N, Kwon Y M , Structure, function and regulation of the DNA-binding protein Dps and its role in acid and oxidative stress resistance in Escherichia coli: a review. Journal of Applied Microbiology, 2011,110(2):375-386.
[41] Adikesavan A K, Katsonis P, Marciano D C , et al. Separation of recombination and SOS response in Escherichia coli RecA suggests LexA interaction sites. PLoS Genetics, 2011,7(9):e1002244.
doi: 10.1371/journal.pgen.1002244 pmid: 21912525
[42] Das S, Ganeriwal S, Mangwani N , et al. Survival and expression of DNA repair genes in marine bacteria Pseudomonas pseudoalcaligenes NP103 and Paeruginosa N6P6 in response to environmental stressors. Microbiology, 2015,84(5):644-653.
[43] Lemme A, Sztajer H, Wagner-Dobler I . Characterization of mleR, a positive regulator of malolactic fermentation and part of the acid tolerance response in Streptococcus mutans. BMC Microbiology, 2010,10(1):58.
[44] Liu Y P, Tang H Z, Zhang L L , et al. Mechanisms of acid tolerance in bacteria and prospects in biotechnology and bioremediation. Biotechnology Advances, 2015,33(7):1484-1492.
pmid: 26057689
[45] 刘仲汇, 冯东, 冯德荣 , 等. pH值与温度智能控制系统在生物肥发酵中的应用. 农业工程学报, 2005,21(8):187-189.
Liu Z H, Feng D, Feng D R , et al. Application of pH-temperature intelligent control system for fermentation of bio-fertilizer. Transactions of the Chinese Society of Agricultural Engineering, 2005,21(8):187-189.
[46] Portnoy V A, Bezdan D, Zengler K . Adaptive laboratory evolution-harnessing the power of biology for metabolic engineering. Current Opin Biotechnol, 2011,22(4):590-594.
[47] Caspeta L, Chen Y, Nielsen J . Thermo-tolerant yeasts selected by adaptive evolution express heat stress response at 30℃. SCI Rep, 2016,6(1):27003.
[48] Shinichi O, Wataru G, Yasuhiro M , et al. Thermal and solvent stress cross-tolerance conferred to Corynebacterium glutamicum by adaptive laboratory evolution. Applied and Environmental Microbiology, 2015,81(7):2284-2298.
doi: 10.1128/AEM.03973-14 pmid: 25595768
[49] Zhang J, Wu C, Du G , et al. Enhanced acid tolerance in Lactobacillus casei by adaptive evolution and compared stress response during acid stress. Biotechnology and Bioprocess Engineering, 2012,17(2):283-289.
[50] Park, Hyun J, Joo H , et al. Low-pH production of D-lactic acid using newly isolated acid tolerant yeast Pichia kudriavzevii NG7. Biotechnology and Bioengineering, 2018,115(9):2232-2242.
[51] Wrighton K H . Synthetic biology: Multiplex genome engineering in eukaryotes. Nature Reviews Genetics, 2018,19(1):6.
doi: 10.1038/nrg.2017.99 pmid: 29129919
[52] Teixeira M C, Godinho C P, Cabrito T R , et al. Increased expression of the yeast multidrug resistance ABC transporter Pdr18 leads to increased ethanol tolerance and ethanol production in high gravity alcoholic fermentation. Microbial Cell Factories, 2012,11(1):98.
[53] Liu Y, Zhang G, Sun H , et al. Enhanced pathway efficiency of Saccharomyces cerevisiae by introducing thermo-tolerant devices. Bioresource Technology, 2014,170:38-44.
pmid: 25118151
[54] Liu D, Du J, Zhao G , et al. Applications of synthetic biology in medicine and energy. CIESC Journal, 2011,62(9):2391-2397.
[55] Pham H L, Wong A, Chua N , et al. Engineering a riboswitch-based genetic platform for the self-directed evolution of acid-tolerant phenotypes. Nature Communications, 2017,8(1):411.
[56] Darbani B, Stovicek V, Van Der Hoek S A , et al. Engineering energetically efficient transport of dicarboxylic acids in yeast Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences, 2019,116(39):19415-19420.
[57] Gaj T, Gersbach C A, Barbas C F . ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends in Biotechnology, 2013,31(7):397-405.
pmid: 23664777
[58] Li W, Teng F, Li T , et al. Simultaneous generation and germline transmission of multiple gene mutations in rat using CRISPR-Cas systems. Nature Biotechnology, 2013,31(8):684.
[59] Hsu P D, Lander E S, Zhang F , et al. Development and applications of CRISPR-Cas9 for genome engineering. Cell, 2014,157(6):1262-1278.
pmid: 24906146
[60] Mitsui R, Yamada R, Ogino H . Improved stress tolerance of Saccharomyces cerevisiae by CRISPR-Cas-Mediated genome evolution. Applied Biochemistry and Biotechnology, 2019,189:810-812.
doi: 10.1007/s12010-019-03040-y
[61] Ma L, Li Y, Chen X , et al. SCRaMbLE generates evolved yeasts with increased alkali tolerance. Microbial Cell Factories, 2019,18(1):52.
pmid: 30857530
[1] 陈晨, 邰超, 李霜. 米根霉发酵产富马酸的最适替代中和剂及pH调控策略研究[J]. 中国生物工程杂志, 2013, 33(4): 85-91.
[2] 柯为. 遗传工程改造氨基酸产生菌取得新进展——苏联获得产苏氨酸高产菌种居领先地位[J]. 中国生物工程杂志, 1982, 2(3): 47-47.
[3] G.Schikora, 罗迪安. 生物技术的新途径——DNA重组的应用已进入工业大门[J]. 中国生物工程杂志, 1982, 2(1): 79-81.
[4] 罗明典. 苏联基因工程研究的成就[J]. 中国生物工程杂志, 1981, 1(3): 57-57.
[5] 石吕平. 工业遗传工程迅速发展[J]. 中国生物工程杂志, 1981, 1(2): 56-57.